<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/NCT03255083</url>
  </required_header>
  <id_info>
    <org_study_id>DS1205-A-U101</org_study_id>
    <nct_id>NCT03255083</nct_id>
  </id_info>
  <brief_title>DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer</brief_title>
  <official_title>A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Osimertinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study has two parts: dose escalation and dose expansion.&#xD;
&#xD;
      The primary objectives are:&#xD;
&#xD;
        -  For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined&#xD;
           with osimertinib in the study population and to determine the recommended dose for&#xD;
           expansion of DS-1205c when combined with osimertinib in the study population&#xD;
&#xD;
        -  For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with&#xD;
           osimertinib in the study population&#xD;
&#xD;
      In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle&#xD;
      1 onward). In Dose Expansion, there will be 21-day cycles.&#xD;
&#xD;
      The number of treatment cycles is not fixed in this study. Participants will continue study&#xD;
      treatment until they decide not to (withdraw consent), their disease gets worse [progressive&#xD;
      disease (PD)], or side effects become unacceptable (unacceptable toxicity).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This study was terminated based on a business decision by the Sponsor.&#xD;
  </why_stopped>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Actual">September 4, 2020</completion_date>
  <primary_completion_date type="Actual">September 4, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)</time_frame>
    <description>A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
    <description>Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
    <description>Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
    <description>Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
    <description>Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib</measure>
    <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
    <description>Overall survival was defined as the time from the date of first dose to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
    <description>The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
    <description>The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
    <description>The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
    <description>The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
    <description>The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Non-small Cell Lung Cancer (NSCLC)</condition>
  <arm_group>
    <arm_group_label>DS-1205c with osimertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1200 mg) in combination with daily 80 mg oral dose of osimertinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-1205c</intervention_name>
    <description>DS-1205c 200 mg capsule</description>
    <arm_group_label>DS-1205c with osimertinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>Osimertinib 80 mg tablet</description>
    <arm_group_label>DS-1205c with osimertinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has histologically or cytologically documented adenocarcinoma NSCLC.&#xD;
&#xD;
          2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or&#xD;
             radiation.&#xD;
&#xD;
          3. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID:&#xD;
             19949011):&#xD;
&#xD;
               1. Historical confirmation that the tumor harbors an EGFR mutation known to be&#xD;
                  associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R,&#xD;
                  L861Q) or&#xD;
&#xD;
               2. Has experienced clinical benefit from an EGFR TKI, followed by systemic&#xD;
                  progression (Response Evaluation Criteria in Solid Tumors [RECIST version 1.1] or&#xD;
                  World Health Organization [WHO]) while on continuous treatment with an EGFR TKI.&#xD;
&#xD;
          4. Is currently receiving, and is able to discontinue erlotinib, gefinitib, or afatinib;&#xD;
             or is currently receiving osimertinib at the prescribed 80 mg dose and is able to&#xD;
             interrupt osimertinib.&#xD;
&#xD;
          5. Has been receiving erlotinib, gefitinib, or afatinib for at least 6 weeks with&#xD;
             well-controlled related toxicities less than Grade 3 in severity at the time of&#xD;
             screening period.&#xD;
&#xD;
          6. Has radiological documentation of disease progression while receiving continuous&#xD;
             treatment with erlotinib, gefitinib, afatinib, or osimertinib.&#xD;
&#xD;
          7. Has at least one measurable lesion per RECIST version 1.1.&#xD;
&#xD;
          8. Is willing to provide archival tumor tissue from a biopsy performed after progression&#xD;
             during treatment with erlotinib, gefitinib, afatinib , or osimertinib OR has at least&#xD;
             one lesion not previously irradiated, amenable to core biopsy, and is willing to&#xD;
             undergo screening tumor biopsy.&#xD;
&#xD;
          9. Demonstrates absence of EGFR T790M. No EGFR mutation testing is required if treated&#xD;
             with osimertinib.&#xD;
&#xD;
         10. Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with&#xD;
             no deterioration over the previous 2 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has any evidence of small cell histology, or combined small cell and non-small cell&#xD;
             histology, in original tumor biopsy or in screening biopsy performed since&#xD;
             progression.&#xD;
&#xD;
          2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS&#xD;
             proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection&#xD;
             (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET&#xD;
             exon 14 skipping mutation. No new testing for these genomic alterations is required&#xD;
             for Screening.&#xD;
&#xD;
          3. Has received treatment with any of the following:&#xD;
&#xD;
               1. Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, investigational&#xD;
                  agent or other anticancer drug(s) from a previous cancer treatment regimen or&#xD;
                  clinical study (other than EGFR TKI), within 14 days of the first dose of study&#xD;
                  treatment.&#xD;
&#xD;
               2. Immune checkpoint inhibitor therapy within 30 days of first dose of study&#xD;
                  treatment.&#xD;
&#xD;
               3. Major surgery (excluding placement of vascular access) within 4 weeks of the&#xD;
                  first dose of study treatment.&#xD;
&#xD;
               4. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field&#xD;
                  of radiation within 4 weeks, or palliative radiation therapy within 2 weeks of&#xD;
                  the first dose of study drug treatment.&#xD;
&#xD;
          4. Has history of other active malignancy within 3 years prior to enrollment, except:&#xD;
&#xD;
               1. Adequately treated non-melanoma skin cancer OR&#xD;
&#xD;
               2. Superficial bladder tumors (tumor stage &quot;a&quot; [Ta], tumor stage &quot;is&quot; [Tis], tumor&#xD;
                  stage &quot;1&quot; [T1]) OR&#xD;
&#xD;
               3. Curatively treated in situ disease OR&#xD;
&#xD;
               4. Low risk non-metastatic prostate cancer (with Gleason score &lt; 7, and following&#xD;
                  local treatment or undergoing active surveillance)&#xD;
&#xD;
          5. Has spinal cord compression or clinically active brain metastases, defined as&#xD;
             untreated and symptomatic, or requiring therapy with corticosteroids or&#xD;
             anticonvulsants to control associated symptoms. Subjects with clinically inactive&#xD;
             brain metastases may be included in the study. Subjects with treated brain metastases&#xD;
             that are no longer symptomatic and who require no treatment with corticosteroids or&#xD;
             anticonvulsants may be included in the study if they have recovered from the acute&#xD;
             toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end&#xD;
             of whole brain radiotherapy and study enrollment (1 week for stereotactic&#xD;
             radiotherapy).&#xD;
&#xD;
          6. Presence of retinal disease in the eye that is not due to neovascular age-related&#xD;
             macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal&#xD;
             atrophy, retinal detachment).&#xD;
&#xD;
          7. Has history of myocardial infarction within the past 6 months.&#xD;
&#xD;
          8. Has symptomatic congestive heart failure (New York Heart Association [NYHA] Classes&#xD;
             II-IV), unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment.&#xD;
&#xD;
          9. Has left ventricular ejection fraction (LVEF) &lt;45% by either echocardiogram (ECHO) or&#xD;
             multigated acquisition (MUGA) scan.&#xD;
&#xD;
         10. Has any clinically important abnormalities in rhythm, conduction or morphology of&#xD;
             resting ECG, eg, complete left bundle branch block, third-degree heart block,&#xD;
             second-degree heart block, or PR interval &gt;250 milliseconds (ms).&#xD;
&#xD;
         11. Has a mean QT interval corrected using Fridericia's correction (QTcF) prolongation&#xD;
             &gt;470 ms for females and &gt;450 ms for males in three successive Screening measurements.&#xD;
&#xD;
         12. Unable or unwilling to discontinue concomitant use of drugs that are known to prolong&#xD;
             the QT interval.&#xD;
&#xD;
         13. Has any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
             events, such as congenital long QT syndrome, family history of long QT syndrome or&#xD;
             unexplained sudden death under 40 years of age in first degree relatives.&#xD;
&#xD;
         14. Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation&#xD;
             pneumonitis) or is suspected to have such disease by imaging during screening.&#xD;
&#xD;
         15. Has history of pancreatitis within the past 6 months.&#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>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Taipei Medical University, Shuang Ho Hospital</name>
      <address>
        <city>New Taipei City</city>
        <zip>23561</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng-Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>70457</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10048</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11031</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, Lynch T, Johnson BE, Miller VA. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010 Jan 10;28(2):357-60. doi: 10.1200/JCO.2009.24.7049. Epub 2009 Nov 30.</citation>
    <PMID>19949011</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <results_first_submitted>August 30, 2021</results_first_submitted>
  <results_first_submitted_qc>November 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 11, 2022</results_first_posted>
  <last_update_submitted>January 10, 2022</last_update_submitted>
  <last_update_submitted_qc>January 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oncology</keyword>
  <keyword>Advanced Non-small Cell Lung Cancer</keyword>
  <keyword>Inoperable Non-small Cell Lung Cancer</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Non-resectable</keyword>
  <keyword>Epidermal growth factor receptor</keyword>
  <keyword>EGFR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 5, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03255083/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 13 participants who met all inclusion criteria and no exclusion criteria were enrolled from 10 April 2019 to 04 September 2020 in the study at 7 clinical sites in Taiwan.</recruitment_details>
      <pre_assignment_details>In the dose escalation phase, the recommended dose for expansion of DS-1205c in combination with a fixed dose of osimertinib was assessed. The doses of DS-1205c selected for this study were based on nonclinical data and were expressed in doses of DS-1205a (free base).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>DS-1205c 200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="P2">
          <title>DS-1205c 400 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="P3">
          <title>DS-1205c 800 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="P4">
          <title>DS-1205c 1200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</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="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Clinical progression</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease by RECIST version 1.1</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Demographic and baseline characteristics were assessed in the Full Analysis Set.</population>
      <group_list>
        <group group_id="B1">
          <title>DS-1205c 200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="B2">
          <title>DS-1205c 400 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="B3">
          <title>DS-1205c 800 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="B4">
          <title>DS-1205c 1200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="B5">
          <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="6"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="1"/>
            <count group_id="B5" value="13"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.5" lower_limit="45" upper_limit="77"/>
                    <measurement group_id="B2" value="73.0" lower_limit="61" upper_limit="88"/>
                    <measurement group_id="B3" value="64.0" lower_limit="63" upper_limit="68"/>
                    <measurement group_id="B4" value="70" lower_limit="70" upper_limit="70"/>
                    <measurement group_id="B5" value="64.0" lower_limit="45" upper_limit="88"/>
                  </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="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Taiwan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib</title>
        <description>A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.</description>
        <time_frame>Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)</time_frame>
        <population>Dose-limiting toxicities were assessed in the Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib</title>
          <description>A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.</description>
          <population>Dose-limiting toxicities were assessed in the Safety Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib</title>
        <description>Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.</description>
        <time_frame>Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
        <population>Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib</title>
          <description>Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.</description>
          <population>Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Upper respiratory tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cough</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnoea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Haemoptysis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhoea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pyrexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Creatinine Phosphokinase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Creatinine Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ejection Fraction Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lipase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overdose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
        <description>Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.</description>
        <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
        <population>Best overall response was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
          <description>Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.</description>
          <population>Best overall response was assessed in the Full Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response (CR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease (PD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not evaluable (NE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall response rate (ORR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
        <description>Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.</description>
        <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
        <population>Disease control rate was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
          <description>Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.</description>
          <population>Disease control rate was assessed in the Full Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
        <description>Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.</description>
        <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
        <population>Progression-free survival was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib</title>
          <description>Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.</description>
          <population>Progression-free survival was assessed in the Full Analysis Set.</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" lower_limit="5.4" upper_limit="36.6"/>
                    <measurement group_id="O2" value="NA" lower_limit="12.3" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event. The estimated upper bound of 95% confidence interval is essentially infinity, therefore it is also N/A.</measurement>
                    <measurement group_id="O3" value="22.0" lower_limit="12.1" upper_limit="22.0"/>
                    <measurement group_id="O4" value="12.4" lower_limit="NA" upper_limit="NA">Not enough sample size to estimate a standard error for the median survival time so the 95% confidence interval bounds are N/A.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib</title>
        <description>Overall survival was defined as the time from the date of first dose to the date of death due to any cause.</description>
        <time_frame>Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year</time_frame>
        <population>Overall survival was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib</title>
          <description>Overall survival was defined as the time from the date of first dose to the date of death due to any cause.</description>
          <population>Overall survival was assessed in the Full Analysis Set.</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.9" lower_limit="34.0" upper_limit="NA">The estimated upper bound of 95% confidence interval is essentially infinity, therefore it is N/A.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="14" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event. The estimated upper bound of 95% confidence interval is essentially infinity, therefore it is also N/A.</measurement>
                    <measurement group_id="O3" value="NA" lower_limit="32" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event. The estimated upper bound of 95% confidence interval is essentially infinity, therefore it is also N/A.</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">Not enough sample size to estimate a standard error for the median survival time so the median and 95% confidence interval bounds are both N/A.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
        <description>The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
        <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
          <description>The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
          <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</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 group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="292" spread="94.8"/>
                    <measurement group_id="O2" value="413" spread="94.0"/>
                    <measurement group_id="O3" value="499" spread="222"/>
                    <measurement group_id="O4" value="703" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="561" spread="191"/>
                    <measurement group_id="O2" value="827" spread="299"/>
                    <measurement group_id="O3" value="1041" spread="460"/>
                    <measurement group_id="O4" value="1070" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="544" spread="176"/>
                    <measurement group_id="O2" value="845" spread="328"/>
                    <measurement group_id="O3" value="921" spread="260"/>
                    <measurement group_id="O4" value="1150" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
        <description>The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
        <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
          <description>The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
          <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</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 group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUClast, Cycle 0: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1916" spread="530"/>
                    <measurement group_id="O2" value="2493" spread="277"/>
                    <measurement group_id="O3" value="2891" spread="1398"/>
                    <measurement group_id="O4" value="5050" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUClast, Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4193" spread="1514"/>
                    <measurement group_id="O2" value="5716" spread="1931"/>
                    <measurement group_id="O3" value="7385" spread="4562"/>
                    <measurement group_id="O4" value="8602" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUClast, Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4445" spread="1389"/>
                    <measurement group_id="O2" value="6852" spread="2716"/>
                    <measurement group_id="O3" value="7220" spread="2629"/>
                    <measurement group_id="O4" value="9495" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCtau, Cycle 0: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1975" spread="563"/>
                    <measurement group_id="O2" value="2557" spread="257"/>
                    <measurement group_id="O3" value="3002" spread="1472"/>
                    <measurement group_id="O4" value="5255" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCtau, Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4818" spread="1772"/>
                    <measurement group_id="O2" value="6496" spread="2208"/>
                    <measurement group_id="O3" value="6972" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                    <measurement group_id="O4" value="10300" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCtau, Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4596" spread="1488"/>
                    <measurement group_id="O2" value="7117" spread="2883"/>
                    <measurement group_id="O3" value="7640" spread="2918"/>
                    <measurement group_id="O4" value="10000" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
        <description>The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
        <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
          <description>The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
          <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" lower_limit="2.0" upper_limit="6.0"/>
                    <measurement group_id="O2" value="4.0" lower_limit="3.9" upper_limit="4.0"/>
                    <measurement group_id="O3" value="3.9" lower_limit="2.0" upper_limit="4.0"/>
                    <measurement group_id="O4" value="6.2" lower_limit="6.2" upper_limit="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" lower_limit="2.0" upper_limit="4.2"/>
                    <measurement group_id="O2" value="4.0" lower_limit="2.1" upper_limit="4.0"/>
                    <measurement group_id="O3" value="4.0" lower_limit="3.9" upper_limit="5.9"/>
                    <measurement group_id="O4" value="4.0" lower_limit="4.0" upper_limit="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" lower_limit="4.0" upper_limit="4.2"/>
                    <measurement group_id="O2" value="4.0" lower_limit="2.0" upper_limit="4.1"/>
                    <measurement group_id="O3" value="2.1" lower_limit="0" upper_limit="4.0"/>
                    <measurement group_id="O4" value="3.9" lower_limit="3.9" upper_limit="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
        <description>The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
        <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
          <description>The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
          <population>Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.</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 group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="376" spread="143"/>
                    <measurement group_id="O2" value="460" spread="219"/>
                    <measurement group_id="O3" value="688" spread="631"/>
                    <measurement group_id="O4" value="816" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="359" spread="137"/>
                    <measurement group_id="O2" value="576" spread="275"/>
                    <measurement group_id="O3" value="722" spread="406"/>
                    <measurement group_id="O4" value="903" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
        <description>The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)</time_frame>
        <population>The pharmacokinetic parameter of terminal half-life (t1/2) was assessed in the Pharmacokinetic Analysis Set, except for 1 patient (Cohort 1) who did not have an available sample.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-1205c 200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>DS-1205c 400 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>DS-1205c 800 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>DS-1205c 1200 mg + Osimertinib</title>
            <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib</title>
          <description>The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.</description>
          <population>The pharmacokinetic parameter of terminal half-life (t1/2) was assessed in the Pharmacokinetic Analysis Set, except for 1 patient (Cohort 1) who did not have an available sample.</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="5"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.98" spread="1.89"/>
                    <measurement group_id="O2" value="5.3" spread="1.0"/>
                    <measurement group_id="O3" value="4.7" spread="0.6"/>
                    <measurement group_id="O4" value="3.3" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 0: Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="6.7"/>
                    <measurement group_id="O2" value="7.1" spread="1.0"/>
                    <measurement group_id="O3" value="6.9" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="3.3"/>
                    <measurement group_id="O2" value="7.9" spread="0.8"/>
                    <measurement group_id="O3" value="7.0" spread="1.3"/>
                    <measurement group_id="O4" value="11.7" spread="NA">Due to small sample size, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (TEAEs) were collected at Screening, Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year.</time_frame>
      <desc>A TEAE is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiation of the study drug until 30 days after last dose of the study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>DS-1205c 200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="E2">
          <title>DS-1205c 400 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="E3">
          <title>DS-1205c 800 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
        <group group_id="E4">
          <title>DS-1205c 1200 mg + Osimertinib</title>
          <description>Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.1</default_vocab>
        <default_assessment>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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastases to Meninges</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.1</default_vocab>
        <default_assessment>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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymph node pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Splenomegaly</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cornea verticillata</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastric polyps</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tinea capitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Traumatic haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Spondylolisthesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastases to meninges</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Haemopytsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Breath sounds abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Onychomadesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was terminated based on a business decision by the Sponsor.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Contact for Clinical Trial Information</name_or_title>
      <organization>Daiichi Sankyo</organization>
      <phone>908-992-6400</phone>
      <email>CTRinfo@dsi.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/NCT03255083
org study id: DS1205-A-U101
nct id: NCT03255083
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study has two parts: dose escalation and dose expansion.

      The primary objectives are:

        -  For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined
           with osimertinib in the study population and to determine the recommended dose for
           expansion of DS-1205c when combined with osimertinib in the study population

        -  For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with
           osimertinib in the study population

      In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle
      1 onward). In Dose Expansion, there will be 21-day cycles.

      The number of treatment cycles is not fixed in this study. Participants will continue study
      treatment until they decide not to (withdraw consent), their disease gets worse [progressive
      disease (PD)], or side effects become unacceptable (unacceptable toxicity).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib
time frame: Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)
description: A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.
measure: Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib
time frame: Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year
description: Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.
measure: Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
description: Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.
measure: Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
description: Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
measure: Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
description: Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.
measure: Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib
time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
description: Overall survival was defined as the time from the date of first dose to the date of death due to any cause.
measure: Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
description: The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
measure: Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib
time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
description: The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
measure: Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
description: The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
measure: Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib
time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
description: The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
measure: Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib
time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
description: The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
arm group label: DS-1205c with osimertinib
arm group type: Experimental
description: Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1200 mg) in combination with daily 80 mg oral dose of osimertinib
intervention type: Drug
intervention name: DS-1205c
description: DS-1205c 200 mg capsule
arm group label: DS-1205c with osimertinib
intervention type: Drug
intervention name: Osimertinib
description: Osimertinib 80 mg tablet
arm group label: DS-1205c with osimertinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
country: France
country: United States
citation: Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, Lynch T, Johnson BE, Miller VA. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010 Jan 10;28(2):357-60. doi: 10.1200/JCO.2009.24.7049. Epub 2009 Nov 30.
PMID: 19949011
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Osimertinib
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was terminated based on a business decision by the Sponsor.
point of contact: 