<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/NCT02999672</url>
  </required_header>
  <id_info>
    <org_study_id>MO29694</org_study_id>
    <secondary_id>2015-001377-40</secondary_id>
    <nct_id>NCT02999672</nct_id>
  </id_info>
  <brief_title>A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors</brief_title>
  <acronym>KAMELEON</acronym>
  <official_title>Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and&#xD;
      pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally&#xD;
      advanced (unresectable and not treatable with curative intent) or metastatic urothelial&#xD;
      bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent)&#xD;
      or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no&#xD;
      longer possible and where no other treatment options are available anymore. Participants will&#xD;
      receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per&#xD;
      kilogram [mg/kg], weekly [qw]) or Regimen B (3.6 mg/kg, every 3 weeks [q3w]) until&#xD;
      unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever&#xD;
      occurs first. Based on tolerability and safety aspects, steering committee and Independent&#xD;
      Data Monitoring Committee (iDMC) will decide on expansion of the study to include more&#xD;
      participants with other carcinoma types.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 23, 2016</start_date>
  <completion_date type="Actual">April 10, 2018</completion_date>
  <primary_completion_date type="Actual">April 10, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).</measure>
    <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
    <description>BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [&lt;] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
    <description>PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
    <description>OS was determined as the time from beginning of treatment to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)</measure>
    <time_frame>Baseline up to approximately 18 months</time_frame>
    <description>Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria</measure>
    <time_frame>Baseline up to approximately 18 months</time_frame>
    <description>Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma/Serum Concentrations of Trastuzumab Emtansine</measure>
    <time_frame>Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days</time_frame>
    <description>Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Bladder Cancer</condition>
  <condition>Pancreas Cancer</condition>
  <condition>Cholangiocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort 1 (UBC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC will initially receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 (Pancreatic cancer/cholangiocarcinoma)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma will receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab Emtansine</intervention_name>
    <description>Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.</description>
    <arm_group_label>Cohort 1 (UBC)</arm_group_label>
    <arm_group_label>Cohort 2 (Pancreatic cancer/cholangiocarcinoma)</arm_group_label>
    <other_name>Kadcyla</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ in&#xD;
             greater than or equal to [&gt;/=] 30 percent [%] of tumor cells): locally advanced&#xD;
             (unresectable and not treatable with curative intent), or metastatic UBC or locally&#xD;
             advanced (unresectable and not treatable with curative intent) or metastatic&#xD;
             pancreatic cancer/cholangiocarcinoma&#xD;
&#xD;
          -  There must be no standard treatment options available for participants with the above&#xD;
             HER2 overexpressing tumors and they must have undergone at least one prior&#xD;
             platinum-based treatment for locally advanced (unresectable and not treatable with&#xD;
             curative intent) or metastatic tumor (Note: for pancreatic cancer/cholangiocarcinoma,&#xD;
             prior treatments are not required to be platinum-based.)&#xD;
&#xD;
          -  Participant's lesion should be measurable according to RECIST V1.1 on diagnostic&#xD;
             computed tomography (CT) scan/magnetic resonance imaging (MRI); Target lesion(s)&#xD;
             should not have been previously irradiated&#xD;
&#xD;
          -  At least one formalin-fixed paraffin-embedded (FFPE) biopsy of the primary tumor&#xD;
             and/or from a metastatic site is required&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2&#xD;
&#xD;
          -  No significant cardiac history and a current left ventricular ejection fraction (LVEF)&#xD;
             &gt;/=50%&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with previous exposure to HER2-targeted therapies in any setting&#xD;
&#xD;
          -  Participants showing histologically confirmed focal HER2-expression, that is, less&#xD;
             than (&lt;) 30% of positively stained tumor cells&#xD;
&#xD;
          -  Participants with brain metastasis as the sole site of metastatic disease and/or are&#xD;
             symptomatic or require therapy to control symptoms&#xD;
&#xD;
          -  Current uncontrolled hypertension (systolic greater than [&gt;] 150 millimeters of&#xD;
             mercury [mmHg] and/or diastolic &gt;100 mmHg)&#xD;
&#xD;
          -  Current unstable angina pectoris&#xD;
&#xD;
          -  History of symptomatic congestive heart failure (CHF) of any New York Heart&#xD;
             Association (NYHA) criteria or ventricular arrhythmia that requires treatment&#xD;
&#xD;
          -  History of myocardial infarction within the last 6 months&#xD;
&#xD;
          -  Peripheral neuropathy, Grade &gt;/=3&#xD;
&#xD;
          -  Current dyspnea at rest due to complications of advanced malignancy, or other diseases&#xD;
             that require continuous oxygen therapy&#xD;
&#xD;
          -  Current severe, uncontrolled systemic disease&#xD;
&#xD;
          -  History of other malignancy within the last 5 years&#xD;
&#xD;
          -  Concurrent, serious, uncontrolled infections or current known infection with human&#xD;
             immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C&#xD;
&#xD;
          -  Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the&#xD;
             excipients of the investigational medicinal product (IMP)&#xD;
&#xD;
          -  Clinically significant bleeding within 30 days before enrollment&#xD;
&#xD;
          -  Major surgical procedure or significant traumatic injury within 28 days prior to&#xD;
             randomization or anticipation of the need for major surgery during the course of study&#xD;
             treatment&#xD;
&#xD;
          -  Concurrent participation in any other therapeutic clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica</name>
      <address>
        <city>Meldola</city>
        <state>Emilia-Romagna</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Ospedale San Raffaele;Oncologia Medica</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima</name>
      <address>
        <city>Padova</city>
        <state>Veneto</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.</name>
      <address>
        <city>Verona</city>
        <state>Veneto</state>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoni van Leeuwenhoek Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC Location VUMC</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCG</name>
      <address>
        <city>NL -groningen</city>
        <zip>9700 RB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC - Centrum</name>
      <address>
        <city>NL -rotterdam</city>
        <zip>3000 CA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodny onkologicky ustav</name>
      <address>
        <city>Bratislava</city>
        <zip>833 10</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Univ Vall d'Hebron; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals; Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario Carlos Haya; Servicio de Oncologia</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Slovakia</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Switzerland</country>
  </removed_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <results_first_submitted>April 8, 2019</results_first_submitted>
  <results_first_submitted_qc>July 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 28, 2019</results_first_posted>
  <last_update_submitted>July 22, 2019</last_update_submitted>
  <last_update_submitted_qc>July 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Ado-Trastuzumab Emtansine</mesh_term>
    <mesh_term>Maytansine</mesh_term>
  </intervention_browse>
  <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>June 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT02999672/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 (UBC)</title>
          <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
          <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1 (UBC)</title>
          <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
          <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
        <group group_id="B3">
          <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="13"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.4" spread="14.1"/>
                    <measurement group_id="B2" value="62.9" spread="7.2"/>
                    <measurement group_id="B3" value="59.3" spread="12.2"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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_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_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="19"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).</title>
        <description>BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [&lt;] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.</description>
        <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).</title>
          <description>BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [&lt;] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
          <units>Percentage of Treated Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.5"/>
                    <measurement group_id="O2" value="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS)</title>
        <description>PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.</description>
        <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS)</title>
          <description>PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
          <units>Months</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="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.20" lower_limit="1.18" upper_limit="4.30"/>
                    <measurement group_id="O2" value="2.58" lower_limit="1.31" upper_limit="9.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS was determined as the time from beginning of treatment to death from any cause.</description>
        <time_frame>Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS was determined as the time from beginning of treatment to death from any cause.</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
          <units>Months</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="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.03" lower_limit="3.75" upper_limit="NA">NA = NE= Not estimable. Upper limit of the 95 percent (%) confidence interval (CI) could not be calculated, as the study was terminated before a sufficient amount of data could be collected for accurate calculation.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="1.45" upper_limit="NA">NA = NE= Not estimable. Median and upper limit of the 95 percent (%) confidence interval (CI) could not be calculated, as the study was terminated before a sufficient amount of data could be collected for accurate calculation.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)</title>
        <description>Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).</description>
        <time_frame>Baseline up to approximately 18 months</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)</title>
          <description>Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7"/>
                    <measurement group_id="O2" value="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1"/>
                    <measurement group_id="O2" value="57.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.8"/>
                    <measurement group_id="O2" value="28.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE greater than Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.8"/>
                    <measurement group_id="O2" value="28.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE related to Trastuzumab Emtansine (TE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6"/>
                    <measurement group_id="O2" value="85.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.2"/>
                    <measurement group_id="O2" value="28.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAE related to TE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE with fatal outcome</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to discontinuation of TE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to modification of TE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.5"/>
                    <measurement group_id="O2" value="57.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE of special interest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAE of special interest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria</title>
        <description>Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.</description>
        <time_frame>Baseline up to approximately 18 months</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria</title>
          <description>Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma/Serum Concentrations of Trastuzumab Emtansine</title>
        <description>Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.</description>
        <time_frame>Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days</time_frame>
        <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 (UBC)</title>
            <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
            <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma/Serum Concentrations of Trastuzumab Emtansine</title>
          <description>Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.</description>
          <population>Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts.</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="13"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Predose, D1C1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Mean and Standard Deviation was not calculated due to below detection level.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Due to low number of participants, standard deviation can not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15-30 min post-infusion, D1C1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.9" spread="16.1"/>
                    <measurement group_id="O2" value="52.3" spread="16.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Predose, D8C1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.27" spread="2.59"/>
                    <measurement group_id="O2" value="5.82" spread="1.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15-30 min post-infusion, D8C1</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_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.4" spread="12.0"/>
                    <measurement group_id="O2" value="50.3" spread="8.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Predose, D15C1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.8" spread="3.78"/>
                    <measurement group_id="O2" value="9.96" spread="NA">Due to low number of participants, standard deviation can not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15-30 min post-infusion, D15C8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.3" spread="8.75"/>
                    <measurement group_id="O2" value="49.2" spread="NA">Due to low number of participants, standard deviation can not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Predose, D1C2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" spread="9.38"/>
                    <measurement group_id="O2" value="2.02" spread="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Predose, D1C4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" spread="8.63"/>
                    <measurement group_id="O2" value="11.7" spread="8.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15-30 min post-infusion, D1C4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" spread="13.6"/>
                    <measurement group_id="O2" value="65.7" spread="10.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to approximately 18 months</time_frame>
      <desc>An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1 (UBC)</title>
          <description>First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)</title>
          <description>First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v21.0</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="7" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Device-related sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v21.0</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="11" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophilia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain, upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="13"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Influenza like Illness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="13"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood phosphorus decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Meralgia paraesthetica</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Affective disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The results represent the data up to primary completion date (10 April 2018). However, due to the early termination, the study was unable to fully address its primary and secondary objectives.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>1-800-821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02999672
org study id: MO29694
secondary id: 2015-001377-40
nct id: NCT02999672
lead sponsor: 
has dmc: Yes
This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and
      pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally
      advanced (unresectable and not treatable with curative intent) or metastatic urothelial
      bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent)
      or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no
      longer possible and where no other treatment options are available anymore. Participants will
      receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per
      kilogram [mg/kg], weekly [qw]) or Regimen B (3.6 mg/kg, every 3 weeks [q3w]) until
      unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever
      occurs first. Based on tolerability and safety aspects, steering committee and Independent
      Data Monitoring Committee (iDMC) will decide on expansion of the study to include more
      participants with other carcinoma types.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
time frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
description: BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [<] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.
measure: Progression-Free Survival (PFS)
time frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
description: PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
measure: Overall Survival (OS)
time frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
description: OS was determined as the time from beginning of treatment to death from any cause.
measure: Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
time frame: Baseline up to approximately 18 months
description: Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).
measure: Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria
time frame: Baseline up to approximately 18 months
description: Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.
measure: Plasma/Serum Concentrations of Trastuzumab Emtansine
time frame: Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days
description: Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.
arm group label: Cohort 1 (UBC)
arm group type: Experimental
description: First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC will initially receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
arm group label: Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
arm group type: Experimental
description: First six participants with metastatic pancreatic cancer/cholangiocarcinoma will receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
intervention type: Drug
intervention name: Trastuzumab Emtansine
description: Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.
arm group label: Cohort 1 (UBC)
arm group label: Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
other name: Kadcyla
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
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country: Italy
country: Netherlands
country: Slovakia
country: Spain
country: Switzerland
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Cholangiocarcinoma
mesh term: Trastuzumab
mesh term: Ado-Trastuzumab Emtansine
mesh term: Maytansine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The results represent the data up to primary completion date (10 April 2018). However, due to the early termination, the study was unable to fully address its primary and secondary objectives.
point of contact: 