<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01702558</url>
  </required_header>
  <id_info>
    <org_study_id>MO28230</org_study_id>
    <secondary_id>2012-001547-46</secondary_id>
    <nct_id>NCT01702558</nct_id>
  </id_info>
  <brief_title>A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (mBC) or HER2-Positive Locally Advanced/Metastatic Gastric Cancer (LA/mGC)</brief_title>
  <acronym>TRAXHER2</acronym>
  <official_title>Phase I Study of the Combination of Trastuzumab Emtansine (T-DM1) and Capecitabine in HER2-Positive Metastatic Breast Cancer and HER2-Positive Locally Advanced/Metastatic Gastric Cancer Patients, Followed by a Randomized, Open-Label Phase II Study of Trastuzumab Emtansine and Capecitabine Versus Trastuzumab Emtansine Alone in HER2-Positive Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in&#xD;
      combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or&#xD;
      HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2&#xD;
      part to explore the efficacy and safety of the combination of Kadcyla and capecitabine&#xD;
      compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment&#xD;
      is until disease progression, intolerable toxicity, withdrawal of consent, or study end.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The sponsor decided to terminate study after 70% of participants had experienced a&#xD;
    progression-free survival event.&#xD;
  </why_stopped>
  <start_date type="Actual">December 3, 2012</start_date>
  <completion_date type="Actual">May 31, 2017</completion_date>
  <primary_completion_date type="Actual">May 31, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)</measure>
    <time_frame>Continuously during Cycle 1 (up to 3 weeks)</time_frame>
    <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (&gt;) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (&lt;) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (&gt;/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100 percent (%).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks)</measure>
    <time_frame>Continuously during Cycle 1 (up to 3 weeks)</time_frame>
    <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</measure>
    <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments &gt;/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to &lt;10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1 (LA/mGC): Percentage of Participants With DLTs</measure>
    <time_frame>Continuously during 3 weeks</time_frame>
    <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)</measure>
    <time_frame>Continuously during 3 weeks</time_frame>
    <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine</measure>
    <time_frame>Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Serum Concentration of Trastuzumab</measure>
    <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
    <description>Trastuzumab was derived from trastuzumab emtansine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause</measure>
    <time_frame>Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Percentage of Participants Who Died of Any Cause</measure>
    <time_frame>Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 (mBC): Overall Survival (OS)</measure>
    <time_frame>Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
    <description>OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</measure>
    <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)</time_frame>
    <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine</measure>
    <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab</measure>
    <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
    <description>Trastuzumab was derived from trastuzumab emtansine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): Cmax of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): t1/2 of Capecitabine</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</measure>
    <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
    <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared [mg/m^2]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 (mBC): T-DM1 + Capecitabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 (mBC): T-DM1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, or study end.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.</description>
    <arm_group_label>Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab emtansine (T-DM1)</intervention_name>
    <description>Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.</description>
    <arm_group_label>Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine</arm_group_label>
    <arm_group_label>Phase 2 (mBC): T-DM1</arm_group_label>
    <arm_group_label>Phase 2 (mBC): T-DM1 + Capecitabine</arm_group_label>
    <other_name>Kadcyla,</other_name>
    <other_name>RO5304020</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab emtansine (T-DM1)</intervention_name>
    <description>Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.</description>
    <arm_group_label>Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine</arm_group_label>
    <other_name>Kadcyla,</other_name>
    <other_name>RO5304020</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine will be administered at the MTD determined in Cohort 1.</description>
    <arm_group_label>Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine</arm_group_label>
    <arm_group_label>Phase 2 (mBC): T-DM1 + Capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Metastatic Breast Cancer&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2&#xD;
&#xD;
          -  Adequate blood cell count&#xD;
&#xD;
          -  Adequate liver, renal, and cardiac function&#xD;
&#xD;
          -  Life expectancy greater than or equal to (&gt;/=) 12 weeks&#xD;
&#xD;
          -  Histologically or cytologically confirmed breast cancer&#xD;
&#xD;
          -  Confirmed HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or in situ&#xD;
             hybridization (ISH)-positive&#xD;
&#xD;
          -  mBC with at least one measurable lesion according to RECIST v1.1&#xD;
&#xD;
          -  Disease progression on at least one prior regimen containing trastuzumab and&#xD;
             chemotherapy either separately or in combination; participants may be eligible to&#xD;
             receive study therapy in first-line setting if trastuzumab and chemotherapy were given&#xD;
             in the neoadjuvant/adjuvant setting&#xD;
&#xD;
          -  Participant must have recovered from previous treatments&#xD;
&#xD;
        Locally Advanced/Metastatic Gastric Cancer&#xD;
&#xD;
          -  ECOG performance status of 0, 1, or 2&#xD;
&#xD;
          -  Adequate blood cell count&#xD;
&#xD;
          -  Adequate liver, renal, and cardiac function&#xD;
&#xD;
          -  Life expectancy &gt;/= 12 weeks&#xD;
&#xD;
          -  Histologically or cytologically confirmed LA/mGC&#xD;
&#xD;
          -  HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or&#xD;
             IHC 2+ and ISH-positive&#xD;
&#xD;
          -  Inoperable LA/mGC&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Metastatic Breast Cancer&#xD;
&#xD;
          -  Prior treatments before first study treatment:&#xD;
&#xD;
               1. Investigational therapy within 28 days or 5 half-lives, whichever is longer&#xD;
&#xD;
               2. Hormonal therapy within 14 days&#xD;
&#xD;
               3. Trastuzumab within 21 days&#xD;
&#xD;
          -  Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab&#xD;
             emtansine-containing study, regardless of whether the patient received trastuzumab&#xD;
             emtansine&#xD;
&#xD;
          -  Prior treatment with capecitabine&#xD;
&#xD;
          -  History of severe or unexpected reactions to fluoropyrimidine or known&#xD;
             hypersensitivity to fluorouracil&#xD;
&#xD;
          -  Related capecitabine contraindications&#xD;
&#xD;
               1. Treatment with sorivudine or chemically-related analogues&#xD;
&#xD;
               2. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or&#xD;
                  glucose-galactose malabsorption&#xD;
&#xD;
               3. Complete absence of dihydropyrimidine dehydrogenase (DPD) activity&#xD;
&#xD;
          -  History of intolerance or hypersensitivity to trastuzumab or murine proteins or any&#xD;
             product component&#xD;
&#xD;
          -  History of exposure to high cumulative doses of anthracyclines&#xD;
&#xD;
          -  Brain metastases that are symptomatic or require radiation, surgery, or steroid&#xD;
             therapy to control symptoms within 28 days before study drug&#xD;
&#xD;
          -  Current peripheral neuropathy of Grade &gt;/=3&#xD;
&#xD;
          -  History of other malignancy within the last 5 years, except for appropriately treated&#xD;
             carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,&#xD;
             or other cancers with a similar outcome&#xD;
&#xD;
          -  Current unstable ventricular arrhythmia requiring treatment&#xD;
&#xD;
          -  History of symptomatic congestive heart failure (CHF)&#xD;
&#xD;
          -  History of myocardial infarction or unstable angina within 6 months prior to study&#xD;
             drug&#xD;
&#xD;
          -  History of left ventricular ejection fraction (LVEF) less than (&lt;) 40% or symptomatic&#xD;
             CHF with previous trastuzumab treatment&#xD;
&#xD;
          -  Severe dyspnea at rest due to complications of advanced malignancy or currently&#xD;
             requiring continuous oxygen therapy&#xD;
&#xD;
          -  Clinically significant malabsorption syndrome or inability to take oral medication&#xD;
&#xD;
          -  Current severe, uncontrolled systemic disease (such as clinically significant&#xD;
             cardiovascular, pulmonary, or metabolic disease)&#xD;
&#xD;
          -  Major surgical procedure or significant traumatic injury within 28 days before&#xD;
             enrollment or anticipation of the need for major surgery during study treatment&#xD;
&#xD;
          -  Current known active infection with human immunodeficiency virus (HIV) or hepatitis B&#xD;
             or C&#xD;
&#xD;
          -  Lapatinib within 14 days before study drug&#xD;
&#xD;
        Locally Advanced/Metastatic Gastric Cancer&#xD;
&#xD;
          -  Same as above, with addition of previous chemotherapy for advanced/metastatic disease&#xD;
             (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed&#xD;
             between completion of adjuvant/neoadjuvant therapy and enrollment into the study)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fundacion Investigar</name>
      <address>
        <city>Caba</city>
        <zip>C1025ABI</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncologico Riojano Integral (CORI)</name>
      <address>
        <city>La Rioja</city>
        <zip>F5300COE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Erasto Gaertner</name>
      <address>
        <city>Curitiba</city>
        <state>PR</state>
        <zip>81520-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Oncologico de Ribeirao Preto - INORP</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>SP</state>
        <zip>14025-270</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*</name>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <state>SP</state>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto do Cancer do Estado de Sao Paulo - ICESP</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>01246-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Paul Papin; Oncologie Medicale.</name>
      <address>
        <city>Angers</city>
        <zip>49055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard; Departement Oncologie Medicale</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmettes; Oncologie Medicale</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie; Oncologie Medicale</name>
      <address>
        <city>Paris</city>
        <zip>75231</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ico Rene Gauducheau; Oncologie</name>
      <address>
        <city>Saint Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onkologische Schwerpunktpraxis Bielefeld; Haemotologie &amp; Internistische onkologie</name>
      <address>
        <city>Bielefeld</city>
        <zip>33604</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heinrich-Heine Universitätsklinik Düsseldorf</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH</name>
      <address>
        <city>Fulda</city>
        <zip>36043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie</name>
      <address>
        <city>Marburg</city>
        <zip>35043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexandras General Hospital of Athens; Oncology Department</name>
      <address>
        <city>Athens</city>
        <zip>115 28</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ General Hosp Heraklion; Medical Oncology</name>
      <address>
        <city>Heraklion</city>
        <zip>711 10</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Patras Medical Oncology</name>
      <address>
        <city>Patras</city>
        <zip>265 04</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo Di Oncologia</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico</name>
      <address>
        <city>Candiolo</city>
        <state>Piemonte</state>
        <zip>10060</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia</name>
      <address>
        <city>Pontedera</city>
        <state>Toscana</state>
        <zip>56025</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital da Luz; Departamento de Oncologia Medica</name>
      <address>
        <city>Lisboa</city>
        <zip>1500-650</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Santa Maria; Servico de Oncologia Medica</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPO do Porto; Servico de Oncologia Medica</name>
      <address>
        <city>Porto</city>
        <zip>4200-072</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ivanovo Regional Oncology Dispensary</name>
      <address>
        <city>Ivanovo</city>
        <zip>153040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blokhin Cancer Research Center; Combined Treatment</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Oncology Hospital</name>
      <address>
        <city>Moscow</city>
        <zip>143423</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Oncology Dispensary</name>
      <address>
        <city>St Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bashkirian Republican Clinical Oncology Dispensary</name>
      <address>
        <city>UFA</city>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for Oncology and Radiology of Serbia; Medical Oncology</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Centre Nis, Clinic for Oncology</name>
      <address>
        <city>Nis</city>
        <zip>18000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A</name>
      <address>
        <city>Bratislava</city>
        <zip>833 10</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultna nemocnica Trencín; Onkologicke odd.</name>
      <address>
        <city>Trencin</city>
        <zip>911 71</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Univ Vall d'Hebron; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Slovakia</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Lebanon</country>
    <country>Peru</country>
  </removed_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <results_first_submitted>May 28, 2018</results_first_submitted>
  <results_first_submitted_qc>January 8, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 8, 2019</results_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Ado-Trastuzumab Emtansine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT01702558/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT01702558/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 234 participants were screened, out of which, 182 participants were enrolled into the study. Out of the 182 enrolled participants, 3 participants were excluded from all safety and efficacy analyses because they did not sign correct Informed Consent Form (ICF).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine (Cape) at a dose level (DL) of 750 milligrams per meter squared (mg/m^2) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="P2">
          <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="P3">
          <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="P4">
          <title>Phase 2 (mBC): T-DM1 + Cape</title>
          <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="P5">
          <title>Phase 2 (mBC): T-DM1</title>
          <description>In Phase 2, participants (with mBC) who were randomized in this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="81"/>
                <participants group_id="P5" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="34"/>
                <participants group_id="P5" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="47"/>
                <participants group_id="P5" count="42"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="16"/>
                <participants group_id="P5" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Safety Follow-Up less than 3 Months</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="16"/>
                <participants group_id="P5" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety population: Participants who received &gt;/=1 dose of study drug, analyzed as per actual treatment received. In Phase 2, of 161 participants, 1 was randomized in error(received no treatment) and was excluded from safety analysis and 1 who was randomized to T-DM1 alone Arm received Capecitabine throughout study and was counted in T-DM1+Cape Arm.</population>
      <group_list>
        <group group_id="B1">
          <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="B2">
          <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="B3">
          <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="B4">
          <title>Phase 2 (mBC): T-DM1 + Cape</title>
          <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="B5">
          <title>Phase 2 (mBC): T-DM1</title>
          <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="82"/>
            <count group_id="B5" value="78"/>
            <count group_id="B6" value="178"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.9" spread="10.75"/>
                    <measurement group_id="B2" value="50.8" spread="7.76"/>
                    <measurement group_id="B3" value="60.0" spread="7.40"/>
                    <measurement group_id="B4" value="53.3" spread="11.69"/>
                    <measurement group_id="B5" value="52.6" spread="11.19"/>
                    <measurement group_id="B6" value="53.2" spread="11.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="81"/>
                    <measurement group_id="B5" value="78"/>
                    <measurement group_id="B6" value="170"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Race: Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="71"/>
                    <measurement group_id="B5" value="65"/>
                    <measurement group_id="B6" value="152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race: N/A (as per local regulation)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race: Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race: Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race: Mixed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: Hispanic/Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: Chinese</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="39"/>
                    <measurement group_id="B5" value="35"/>
                    <measurement group_id="B6" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: N/A (as per local regulation)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="29"/>
                    <measurement group_id="B6" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity: Mixed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)</title>
        <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (&gt;) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (&lt;) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (&gt;/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100 percent (%).</description>
        <time_frame>Continuously during Cycle 1 (up to 3 weeks)</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort, which included all enrolled and treated mBC participants who did not experience any major protocol deviation and completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)</title>
          <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (&gt;) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (&lt;) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (&gt;/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100 percent (%).</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort, which included all enrolled and treated mBC participants who did not experience any major protocol deviation and completed Cycle 1.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks)</title>
        <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
        <time_frame>Continuously during Cycle 1 (up to 3 weeks)</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1: T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 or 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks)</title>
          <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days (&gt;7 days for DL 1); for DL -1 only: &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort.</population>
          <units>mg/m^2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments &gt;/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to &lt;10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach.</description>
        <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on Intent-to-Treat (ITT) Population, which included all participants in the randomized Phase 2 part of the study. Participants were analyzed as per the initial randomization. Participants without tumor assessment after start of study treatment were considered as non-responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments &gt;/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to &lt;10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach.</description>
          <population>Analysis was performed on Intent-to-Treat (ITT) Population, which included all participants in the randomized Phase 2 part of the study. Participants were analyzed as per the initial randomization. Participants without tumor assessment after start of study treatment were considered as non-responders.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.4" lower_limit="35.0" upper_limit="54.2"/>
                    <measurement group_id="O2" value="36.3" lower_limit="27.3" upper_limit="46.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.336</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in Response Rates</param_type>
            <param_value>8.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.5</ci_lower_limit>
            <ci_upper_limit>20.9</ci_upper_limit>
            <estimate_desc>90% CI was estimated using Hauck-Anderson approach.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1 (LA/mGC): Percentage of Participants With DLTs</title>
        <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
        <time_frame>Continuously during 3 weeks</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort, which included all enrolled and treated LA/mGC participants who did not experience any major protocol deviation and completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Percentage of Participants With DLTs</title>
          <description>A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort, which included all enrolled and treated LA/mGC participants who did not experience any major protocol deviation and completed Cycle 1.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)</title>
        <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
        <time_frame>Continuously during 3 weeks</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)</title>
          <description>MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting &gt;7 consecutive days; febrile neutropenia with ANC &lt;1000 cells/mm^3; Grade &gt;/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade &gt;/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for &gt;14 days; &lt;14 full doses of capecitabine; Cycle 2 dose level &lt;100%.</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort.</population>
          <units>mg/m^2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
        <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.3"/>
                    <measurement group_id="O2" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine</title>
        <time_frame>Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
        <population>Phase 1 pharmacokinetic (PK) analysis population for mBC cohort; included all mBC participants receiving at least one dose of study medication during Phase 1 and had at least one reported serum/plasma result for PK. The PK analysis in mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine</title>
          <population>Phase 1 pharmacokinetic (PK) analysis population for mBC cohort; included all mBC participants receiving at least one dose of study medication during Phase 1 and had at least one reported serum/plasma result for PK. The PK analysis in mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>micrograms per milliliter (mcg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.3" spread="13.3"/>
                    <measurement group_id="O2" value="78.6" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Pre-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17" spread="1.25"/>
                    <measurement group_id="O2" value="2.1" spread="1.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.5" spread="13.3"/>
                    <measurement group_id="O2" value="78.5" spread="14.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Serum Concentration of Trastuzumab</title>
        <description>Trastuzumab was derived from trastuzumab emtansine.</description>
        <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Serum Concentration of Trastuzumab</title>
          <description>Trastuzumab was derived from trastuzumab emtansine.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>mcg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.1" spread="24.37"/>
                    <measurement group_id="O2" value="92.9" spread="22.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Pre-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" spread="13.28"/>
                    <measurement group_id="O2" value="14.0" spread="12.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.8" spread="18.89"/>
                    <measurement group_id="O2" value="94.7" spread="24.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine</title>
        <description>Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine</title>
          <description>Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>nanograms per milliliter (ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2990" spread="38.4"/>
                    <measurement group_id="O2" value="5652" spread="91.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine</title>
        <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine</title>
          <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>hours*nanograms per milliliter (h*ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3973" spread="38.0"/>
                    <measurement group_id="O2" value="5440" spread="57.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine</title>
        <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine</title>
          <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.70" spread="131.9"/>
                    <measurement group_id="O2" value="0.39" spread="38.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" spread="49.9"/>
                    <measurement group_id="O2" value="143" spread="45.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="257" spread="49.9"/>
                    <measurement group_id="O2" value="244" spread="38.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="39.5"/>
                    <measurement group_id="O2" value="0.64" spread="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
        <time_frame>Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
          <population>Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.10" lower_limit="1.2" upper_limit="10.8"/>
                    <measurement group_id="O2" value="2.10" lower_limit="1.9" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method.</description>
        <time_frame>From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method.</description>
          <population>Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.30" lower_limit="8.61" upper_limit="NA">Upper limit of 90% CI could not be calculated due to insufficient number of participants who had an event.</measurement>
                    <measurement group_id="O2" value="12.22" lower_limit="8.84" upper_limit="15.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
        <time_frame>Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.2"/>
                    <measurement group_id="O2" value="70.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method.</description>
        <time_frame>Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.38" lower_limit="7.85" upper_limit="12.91"/>
                    <measurement group_id="O2" value="10.32" lower_limit="7.56" upper_limit="13.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
        <time_frame>Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.8"/>
                    <measurement group_id="O2" value="83.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1</title>
        <description>TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method.</description>
        <time_frame>Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1</title>
          <description>TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.86" lower_limit="7.62" upper_limit="10.68"/>
                    <measurement group_id="O2" value="7.66" lower_limit="6.54" upper_limit="10.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
        <time_frame>Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.9"/>
                    <measurement group_id="O2" value="73.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method.</description>
        <time_frame>Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.15" lower_limit="7.85" upper_limit="12.55"/>
                    <measurement group_id="O2" value="9.82" lower_limit="7.46" upper_limit="13.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1</title>
        <description>The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach.</description>
        <time_frame>Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1</title>
          <description>The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR: &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: &gt;/=20% relative increase with &gt;/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7" lower_limit="57.1" upper_limit="75.3"/>
                    <measurement group_id="O2" value="62.5" lower_limit="52.7" upper_limit="71.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Percentage of Participants Who Died of Any Cause</title>
        <time_frame>Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Percentage of Participants Who Died of Any Cause</title>
          <population>Analysis was performed on ITT Population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2"/>
                    <measurement group_id="O2" value="26.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2 (mBC): Overall Survival (OS)</title>
        <description>OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients.</description>
        <time_frame>Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)</time_frame>
        <population>Analysis was performed on ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 (mBC): T-DM1 + Cape</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 (mBC): T-DM1</title>
            <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2 (mBC): Overall Survival (OS)</title>
          <description>OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients.</description>
          <population>Analysis was performed on ITT Population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median and 90% CI could not be calculated due to insufficient number of participants who had an event.</measurement>
                    <measurement group_id="O2" value="24.71" lower_limit="24.28" upper_limit="NA">Upper limit of 90% CI could not be calculated due to insufficient number of participants who had an event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</title>
        <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
        <time_frame>Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)</time_frame>
        <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1</title>
          <description>Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to &lt;10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as &gt;/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.</description>
          <population>Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine</title>
        <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine</title>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>mcg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.1" spread="14.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Pre-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.1" spread="5.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.4" spread="7.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab</title>
        <description>Trastuzumab was derived from trastuzumab emtansine.</description>
        <time_frame>Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Serum Concentration of Trastuzumab</title>
          <description>Trastuzumab was derived from trastuzumab emtansine.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>mcg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.1" spread="15.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Pre-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5" spread="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2, Post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.6" spread="13.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): Cmax of Capecitabine</title>
        <description>Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Cmax of Capecitabine</title>
          <description>Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4925" spread="36.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine</title>
        <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine</title>
          <description>AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5131" spread="24.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): t1/2 of Capecitabine</title>
        <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): t1/2 of Capecitabine</title>
          <description>Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.65" spread="34.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137" spread="24.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="213" spread="16.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</title>
        <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
        <time_frame>Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1</time_frame>
        <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
            <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)</title>
          <description>5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.</description>
          <population>Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.83" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Phase 1: Baseline up to 42 days after last dose (up to approximately 1.5 years overall); Phase 2: Baseline up to 42 days after last dose (up to approximately 2.5 years overall)</time_frame>
      <desc>Safety population included all participants who received &gt;/=1 dose of study drug. Participants were analyzed as per actual treatment received. In Phase 2, out of 161 participants, 1 participant was randomized in error (did not receive any treatment) and was excluded from safety analysis and 1 participant who was randomized to T-DM1 alone Arm received Capecitabine throughout study and was counted in T-DM1+Cape Arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="E2">
          <title>Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="E3">
          <title>Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape</title>
          <description>In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="E4">
          <title>Phase 2 (mBC): T-DM1 + Cape</title>
          <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor.</description>
        </group>
        <group group_id="E5">
          <title>Phase 2 (mBC): T-DM1</title>
          <description>In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="18" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="21" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Intestinal haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Mesenteric vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hepatocellular injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Wound sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Radiation necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Fracture displacement</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Brain oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cerebral cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Anuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Uterine polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tumour excision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="75" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="64" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="35" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="21" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Gilbert's syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Deafness unilateral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Middle ear effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Cushingoid</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eye haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blindness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pterygium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Retinal ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="27" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="18" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Anal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Chapped lips</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Glossodynia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Catheter site rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Mucosal dryness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Impaired healing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hepatocellular injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Streptococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Procedural headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Arthropod sting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eye contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Periorbital haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="27" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="31" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="24" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="16" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Liver palpable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cell death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Joint stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Coccydynia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Limb mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Osteonecrosis of jaw</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Weight bearing difficulty</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Aphonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Neurotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vocal cord paralysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Nasal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Nasal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rales</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Macule</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ingrowing nail</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Nail discolouration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Onycholysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash erythematous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin discolouration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Swelling face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Onychoclasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Spider naevus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Skin lesion excision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Tumour excision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Bloody discharge</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The sponsor decided to terminate the study after 70% of participants had experienced a PFS event. Participants were allowed to continue treatment by enrolling into study NCT00781612 or by moving to commercial drug, depending on their country.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01702558
org study id: MO28230
secondary id: 2012-001547-46
nct id: NCT01702558
lead sponsor: 
This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in
      combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or
      HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2
      part to explore the efficacy and safety of the combination of Kadcyla and capecitabine
      compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment
      is until disease progression, intolerable toxicity, withdrawal of consent, or study end.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)
time frame: Continuously during Cycle 1 (up to 3 weeks)
description: A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (>) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (<) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (>/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100 percent (%).
measure: Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks)
time frame: Continuously during Cycle 1 (up to 3 weeks)
description: MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100%.
measure: Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
time frame: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to <10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach.
measure: Phase 1 (LA/mGC): Percentage of Participants With DLTs
time frame: Continuously during 3 weeks
description: A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%.
measure: Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)
time frame: Continuously during 3 weeks
description: MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%.
measure: Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
measure: Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine
time frame: Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
measure: Phase 1 (mBC): Serum Concentration of Trastuzumab
time frame: Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
description: Trastuzumab was derived from trastuzumab emtansine.
measure: Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation.
measure: Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
measure: Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1
time frame: From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method.
measure: Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
measure: Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method.
measure: Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
measure: Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method.
measure: Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause
time frame: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
measure: Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method.
measure: Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
description: The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach.
measure: Phase 2 (mBC): Percentage of Participants Who Died of Any Cause
time frame: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
measure: Phase 2 (mBC): Overall Survival (OS)
time frame: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
description: OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients.
measure: Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
time frame: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)
description: Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
measure: Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine
time frame: Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
measure: Phase 1 (LA/mGC): Serum Concentration of Trastuzumab
time frame: Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
description: Trastuzumab was derived from trastuzumab emtansine.
measure: Phase 1 (LA/mGC): Cmax of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (LA/mGC): t1/2 of Capecitabine
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
measure: Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
time frame: Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1
description: 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
arm group label: Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine
arm group type: Experimental
description: In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared [mg/m^2]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end.
arm group label: Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine
arm group type: Experimental
description: In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.
arm group label: Phase 2 (mBC): T-DM1 + Capecitabine
arm group type: Active Comparator
description: In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.
arm group label: Phase 2 (mBC): T-DM1
arm group type: Experimental
description: In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, or study end.
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.
arm group label: Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine
other name: Xeloda
intervention type: Drug
intervention name: Trastuzumab emtansine (T-DM1)
description: Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
arm group label: Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine
arm group label: Phase 2 (mBC): T-DM1
arm group label: Phase 2 (mBC): T-DM1 + Capecitabine
other name: Kadcyla,
other name: RO5304020
intervention type: Drug
intervention name: Trastuzumab emtansine (T-DM1)
description: Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
arm group label: Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine
other name: Kadcyla,
other name: RO5304020
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine will be administered at the MTD determined in Cohort 1.
arm group label: Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine
arm group label: Phase 2 (mBC): T-DM1 + Capecitabine
other name: Xeloda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Argentina
country: Brazil
country: Canada
country: France
country: Germany
country: Greece
country: Italy
country: Portugal
country: Russian Federation
country: Serbia
country: Slovakia
country: Spain
country: Lebanon
country: Peru
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Stomach Neoplasms
mesh term: Capecitabine
mesh term: Trastuzumab
mesh term: Maytansine
mesh term: Ado-Trastuzumab Emtansine
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limitations and caveats: The sponsor decided to terminate the study after 70% of participants had experienced a PFS event. Participants were allowed to continue treatment by enrolling into study NCT00781612 or by moving to commercial drug, depending on their country.
point of contact: 