<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/NCT03248492</url>
  </required_header>
  <id_info>
    <org_study_id>DS8201-A-U201</org_study_id>
    <secondary_id>2016-004986-18</secondary_id>
    <secondary_id>JapicCTI-173693(en)</secondary_id>
    <secondary_id>DESTINY-Breast01</secondary_id>
    <nct_id>NCT03248492</nct_id>
  </id_info>
  <brief_title>A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)</brief_title>
  <official_title>A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Daiichi Sankyo Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Daiichi Sankyo, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond&#xD;
      or become resistant to current treatment. DS-8201a is a new experimental product that is a&#xD;
      combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may&#xD;
      slow down tumor growth. This might improve outcomes for these patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 25, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">March 21, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
    <description>The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</measure>
    <time_frame>Baseline up to Week 6, 12, 18, 24, 30, 36 post dose</time_frame>
    <description>Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)</measure>
    <time_frame>Day 0 to Day 47 post last dose</time_frame>
    <description>TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">253</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>DS-8201a Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>T-DM1 resistant/refractory (R/R) patients in the low dose treatment group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DS-8201a Medium Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DS-8201a High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>T-DM1 resistant/refractory (R/R) patients in the high dose treatment group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exploratory Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-8201a</intervention_name>
    <description>DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.</description>
    <arm_group_label>DS-8201a High Dose</arm_group_label>
    <arm_group_label>DS-8201a Low Dose</arm_group_label>
    <arm_group_label>DS-8201a Medium Dose</arm_group_label>
    <arm_group_label>Exploratory Arm</arm_group_label>
    <other_name>Experimental product</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women the age of majority in their country&#xD;
&#xD;
          -  Has pathologically documented breast cancer that:&#xD;
&#xD;
               1. is unresectable or metastatic&#xD;
&#xD;
               2. has HER2 positive expression confirmed per protocol&#xD;
&#xD;
          -  Has an adequate tumor sample&#xD;
&#xD;
          -  Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) version 1.1&#xD;
&#xD;
          -  Has protocol-defined adequate cardiac, renal and hepatic function&#xD;
&#xD;
          -  Agrees to follow protocol-defined method(s) of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a medical history of myocardial infarction, symptomatic congestive heart failure&#xD;
             (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia&#xD;
&#xD;
          -  Has a corrected QT interval (QTc) prolongation to &gt; 450 millisecond (ms) in males and&#xD;
             &gt; 470 ms in females&#xD;
&#xD;
          -  Has a medical history of clinically significant lung disease&#xD;
&#xD;
          -  Is suspected to have certain other protocol-defined diseases based on imaging at&#xD;
             screening period&#xD;
&#xD;
          -  Has history of any disease, metastatic condition, drug/medication use or other&#xD;
             condition that might, per protocol or in the opinion of the investigator, compromise:&#xD;
&#xD;
               1. safety or well-being of the participant or offspring&#xD;
&#xD;
               2. safety of study staff&#xD;
&#xD;
               3. analysis of results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alaska Urological Institute dba Alaska Clinical Research Center</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Regents of the University of California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Clinical Oncology Research</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sansum Clinic</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute, LLC</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center - Deerfield Beach</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialist Global Research</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute at Baptist Health, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Straub Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Hawaii</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Healthcare</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville Research Foundation</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists</name>
      <address>
        <city>East Setauket</city>
        <state>New York</state>
        <zip>11733</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aultman Hospital Cancer Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Francis Hospital</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research</name>
      <address>
        <city>Baytown</city>
        <state>Texas</state>
        <zip>77521</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology, P.A.</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Memorial City</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Methodist Hospital Research Institute</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology, P.A. - Longview</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists, PC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Medical Center - Everett</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imeldaziekenhuis</name>
      <address>
        <city>Bonheiden</city>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Hôpital de Charleroi</name>
      <address>
        <city>Charleroi</city>
        <zip>6000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Sart Tilman</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Maarten</name>
      <address>
        <city>Mechelen</city>
        <zip>2800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Sainte Catherine</name>
      <address>
        <city>Avignon</city>
        <zip>84918</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Besançon - Hôpital Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux - Hôpital Saint André</name>
      <address>
        <city>Gironde</city>
        <zip>33075</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de la Rochelle - Hopital St Louis</name>
      <address>
        <city>La Rochelle</city>
        <zip>17019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Victor Hugo - Centre Jean Bernard</name>
      <address>
        <city>Le Mans</city>
        <zip>72015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Nord - CHU Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Régional du Cancer de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Catherine de Sienne</name>
      <address>
        <city>Nantes</city>
        <zip>44202</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Louis - Paris</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRLCC Eugene Marquis</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital d'Instruction des Armees Begin</name>
      <address>
        <city>Saint-Mandé</city>
        <zip>94160</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IEO Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)</name>
      <address>
        <city>Monza</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale degli Infermi</name>
      <address>
        <city>Rimini</city>
        <zip>47923</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona</name>
      <address>
        <city>Torrette</city>
        <zip>60020</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHO Shikoku Cancer Center</name>
      <address>
        <city>Matsuyama</city>
        <state>Ehime-Ken</state>
        <zip>791-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toranomon Hospital</name>
      <address>
        <city>Minato-Ku</city>
        <state>Tokyo-To</state>
        <zip>105-8470</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital</name>
      <address>
        <city>Aichi</city>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Chiba</city>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHO Kyushu Cancer Center</name>
      <address>
        <city>Fukuoka</city>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hakuaikai Sagara Hospital</name>
      <address>
        <city>Kagoshima</city>
        <zip>892-0833</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanagawa Cancer Center</name>
      <address>
        <city>Kanagawa</city>
        <zip>241-0815</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's International Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>104-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Institute Hospital of JFCR</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Chilgok Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si</city>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Cristina</name>
      <address>
        <city>Badajoz</city>
        <zip>6080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Quiron Dexeus</name>
      <address>
        <city>Barcelona</city>
        <zip>08028</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO l´Hospitalet - Hospital Duran i Reynals</name>
      <address>
        <city>Barcelona</city>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Quiron Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>8023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Centre</name>
      <address>
        <city>Madrid</city>
        <zip>28033</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano de Oncologia IVO</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <state>Devon</state>
        <zip>PL6 8BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Mary University of London</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>EC1M 6BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <state>Lothian Region</state>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals City Campus</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Surrey County Hospital</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <zip>GU2 7XX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <results_first_submitted>January 17, 2020</results_first_submitted>
  <results_first_submitted_qc>February 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 17, 2020</results_first_posted>
  <last_update_submitted>October 17, 2022</last_update_submitted>
  <last_update_submitted_qc>October 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER-2 positive breast cancer</keyword>
  <keyword>Metastatic or Unresectable</keyword>
  <keyword>Resistant or refractory to T-DM1</keyword>
  <keyword>DESTINY - Breast 01</keyword>
  <keyword>Trastuzumab deruxtecan</keyword>
  <keyword>T-DXd</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab deruxtecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03248492/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants who met all of the inclusion and none of the exclusion criteria were enrolled and randomized to treatment (Part 1) or received DS-8201a at the recommended dose (Part 2).</recruitment_details>
      <pre_assignment_details>In Part 1, participants were randomized 1:1:1 to either 5.4 mg/kg, 6.4 mg/kg, or 7.4 mg/kg dose of DS-8201a. Two doses randomized 1:1 (6.4 mg/kg and 7.4 mg/kg) were further evaluated. In Part 2, all T-DM1 resistant refractory participants (cohort 2a) or T-DM1 intolerant (cohort 2b) received DS-8201a at the recommended dose.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: DS-8201a Low Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="P2">
          <title>Part 1: DS-8201a Medium Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="P3">
          <title>Part 1: DS-8201a High Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phase.</description>
        </group>
        <group group_id="P4">
          <title>Part 2a: DS-8201a Low Dose</title>
          <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.</description>
        </group>
        <group group_id="P5">
          <title>Part 2b (Exploratory): DS-8201a Low Dose</title>
          <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="48"/>
                <participants group_id="P3" count="21"/>
                <participants group_id="P4" count="130"/>
                <participants group_id="P5" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="48"/>
                <participants group_id="P3" count="21"/>
                <participants group_id="P4" count="130"/>
                <participants group_id="P5" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ongoing</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="85"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease per RECIST v1.1</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="22"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="8"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Part 1: DS-8201a Low Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="B2">
          <title>Part 1: DS-8201a Medium Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="B3">
          <title>Part 1: DS-8201a High Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="B4">
          <title>Part 2a: DS-8201a Low Dose</title>
          <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.</description>
        </group>
        <group group_id="B5">
          <title>Part 2b (Exploratory): DS-8201a Low Dose</title>
          <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
            <count group_id="B2" value="48"/>
            <count group_id="B3" value="21"/>
            <count group_id="B4" value="130"/>
            <count group_id="B5" value="4"/>
            <count group_id="B6" value="253"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="101"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="189"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="29"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="57.9" spread="11.3"/>
                    <measurement group_id="B2" value="55.8" spread="13.0"/>
                    <measurement group_id="B3" value="54.4" spread="10.5"/>
                    <measurement group_id="B4" value="55.4" spread="11.9"/>
                    <measurement group_id="B5" value="49.8" spread="9.2"/>
                    <measurement group_id="B6" value="55.8" spread="11.8"/>
                  </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="50"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="130"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="253"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </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="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="47"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="76"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="132"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>South Korea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="25"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="36"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Objective response rate (ORR) was assessed in the Enrolled Analysis Set.at data cut-off date of 21 March 2019</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 and Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated in Part 1 or Part 2a at the recommended (5.4 mg/kg) dose.</description>
          </group>
          <group group_id="O2">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.</description>
          <population>Objective response rate (ORR) was assessed in the Enrolled Analysis Set.at data cut-off date of 21 March 2019</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="180"/>
                <count group_id="O2" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109"/>
                    <measurement group_id="O2" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Objective response rate (ORR) was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 and Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated in Part 1 or Part 2a at the recommended (5.4 mg/kg) dose.</description>
          </group>
          <group group_id="O2">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.</description>
          <population>Objective response rate (ORR) was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="180"/>
                <count group_id="O2" value="184"/>
                <count group_id="O3" value="48"/>
                <count group_id="O4" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116"/>
                    <measurement group_id="O2" value="118"/>
                    <measurement group_id="O3" value="37"/>
                    <measurement group_id="O4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Best overall tumor response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1 + Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.</description>
          </group>
          <group group_id="O4">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.</description>
          <population>Best overall tumor response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="48"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="180"/>
                <count group_id="O4" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="112"/>
                    <measurement group_id="O4" value="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="59"/>
                    <measurement group_id="O4" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Disease control rate (DCR) and clinical benefit rate (CBR) were assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1 + Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.</description>
          </group>
          <group group_id="O4">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.</description>
          <population>Disease control rate (DCR) and clinical benefit rate (CBR) were assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="48"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="180"/>
                <count group_id="O4" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Disease control rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="175"/>
                    <measurement group_id="O4" value="179"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clinical benefit rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="127"/>
                    <measurement group_id="O4" value="130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Participants with CR or PR were analyzed. Estimated duration of response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1 + Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.</description>
          </group>
          <group group_id="O4">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.</description>
          <population>Participants with CR or PR were analyzed. Estimated duration of response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</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="33"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="109"/>
                <count group_id="O4" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="8.3" upper_limit="NA">There were not enough events to estimate a standard error for the median survival time.</measurement>
                    <measurement group_id="O2" value="6.0" lower_limit="4.8" upper_limit="8.3"/>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event.</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.</description>
        <time_frame>at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)</time_frame>
        <population>Progression-free survival was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1 + Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.</description>
          </group>
          <group group_id="O4">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.</description>
          <population>Progression-free survival was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</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="48"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="180"/>
                <count group_id="O4" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Lack of a median value is due to less than 50% of the participants experiencing the event.</measurement>
                    <measurement group_id="O2" value="9.5" lower_limit="7.4" upper_limit="13.2"/>
                    <measurement group_id="O3" value="NA" lower_limit="10.6" upper_limit="NA">There were not enough events to estimate a standard error for the median survival time.</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="10.6" upper_limit="NA">There were not enough events to estimate a standard error for the median survival time.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
        <description>Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.</description>
        <time_frame>Baseline up to Week 6, 12, 18, 24, 30, 36 post dose</time_frame>
        <population>Best percent change from baseline in sum of diameters was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1 + Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.</description>
          </group>
          <group group_id="O4">
            <title>Part 1 + Part 2a + Part 2b: DS-8201a Low Dose</title>
            <description>All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)</title>
          <description>Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.</description>
          <population>Best percent change from baseline in sum of diameters was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.</population>
          <units>Percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="48"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="180"/>
                <count group_id="O4" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="21"/>
                    <count group_id="O3" value="164"/>
                    <count group_id="O4" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26.2" spread="18.3"/>
                    <measurement group_id="O2" value="-32.9" spread="25.4"/>
                    <measurement group_id="O3" value="-26.9" spread="21.6"/>
                    <measurement group_id="O4" value="-26.9" spread="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="21"/>
                    <count group_id="O3" value="152"/>
                    <count group_id="O4" value="154"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39.6" spread="22.7"/>
                    <measurement group_id="O2" value="-43.6" spread="28.1"/>
                    <measurement group_id="O3" value="-39.9" spread="24.5"/>
                    <measurement group_id="O4" value="-40.1" spread="24.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="136"/>
                    <count group_id="O4" value="138"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-50.1" spread="22.1"/>
                    <measurement group_id="O2" value="-58.5" spread="29.4"/>
                    <measurement group_id="O3" value="-44.4" spread="27.8"/>
                    <measurement group_id="O4" value="-44.9" spread="28.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="124"/>
                    <count group_id="O4" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-56.3" spread="22.1"/>
                    <measurement group_id="O2" value="-61.9" spread="32.0"/>
                    <measurement group_id="O3" value="-49.2" spread="30.6"/>
                    <measurement group_id="O4" value="-49.3" spread="30.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                    <count group_id="O2" value="15"/>
                    <count group_id="O3" value="80"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-59.1" spread="26.1"/>
                    <measurement group_id="O2" value="-63.9" spread="32.2"/>
                    <measurement group_id="O3" value="-51.2" spread="29.2"/>
                    <measurement group_id="O4" value="-51.5" spread="29.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="46"/>
                    <count group_id="O4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-61.0" spread="26.7"/>
                    <measurement group_id="O2" value="-54.6" spread="32.2"/>
                    <measurement group_id="O3" value="-55.5" spread="29.9"/>
                    <measurement group_id="O4" value="-55.5" spread="29.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Best percent change from baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="21"/>
                    <count group_id="O3" value="166"/>
                    <count group_id="O4" value="169"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-59.5" spread="28.2"/>
                    <measurement group_id="O2" value="-65.3" spread="27.7"/>
                    <measurement group_id="O3" value="-50.5" spread="28.3"/>
                    <measurement group_id="O4" value="-50.6" spread="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)</title>
        <description>TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.</description>
        <time_frame>Day 0 to Day 47 post last dose</time_frame>
        <population>Adverse event data were assessed in the Safety Analysis Set t data cut-off date of 21 March 2019.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: DS-8201a Low Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: DS-8201a Medium Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: DS-8201a High Dose</title>
            <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
          </group>
          <group group_id="O4">
            <title>Part 2a: DS-8201a Low Dose</title>
            <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in the continuation phase.</description>
          </group>
          <group group_id="O5">
            <title>Part 2b (Exploratory): DS-8201a Low Dose</title>
            <description>All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in the continuation phase.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)</title>
          <description>TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.</description>
          <population>Adverse event data were assessed in the Safety Analysis Set t data cut-off date of 21 March 2019.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="48"/>
                <count group_id="O3" value="21"/>
                <count group_id="O4" value="130"/>
                <count group_id="O5" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="48"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="129"/>
                    <measurement group_id="O5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="47"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="128"/>
                    <measurement group_id="O5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related TEAEs of CTCAE ≥Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="32"/>
                    <measurement group_id="O3" value="16"/>
                    <measurement group_id="O4" value="48"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="25"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="10"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs associated with drug discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="8"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related TEAEs associated with drug discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="7"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs associated with dose reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="21"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related TEAEs associated with dose reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="20"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs associated with dose interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="12"/>
                    <measurement group_id="O4" value="36"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related TEAEs associated with drug interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="29"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs associated with death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="8"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related TEAEs associated with death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event (AE) data were collected from Day 0 through Day 47 post last dose of study drug.</time_frame>
      <desc>A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part 1: DS-8201a Low Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="E2">
          <title>Part 1: DS-8201a Medium Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="E3">
          <title>Part 1: DS-8201a High Dose</title>
          <description>T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.</description>
        </group>
        <group group_id="E4">
          <title>Part 2a: DS-8201a Low Dose</title>
          <description>All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.</description>
        </group>
        <group group_id="E5">
          <title>Part 2b (Exploratory): DS-8201a Low Dose</title>
          <description>All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in Part 2b in the continuation phase.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="25" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Shock hemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Acute hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Parotitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lymphangitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ilium fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="129" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="31" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Mitral valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="101" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="58" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="46" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="33" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="65" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Odema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion-related reaction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Troponin I increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="37" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="26" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="23" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="61" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nail disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Contact for Clinical Trial Information</name_or_title>
      <organization>Daiichi Sankyo</organization>
      <phone>1-908-992-6400</phone>
      <email>CTRinfo@dsi.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03248492
org study id: DS8201-A-U201
secondary id: 2016-004986-18
secondary id: JapicCTI-173693(en)
secondary id: DESTINY-Breast01
nct id: NCT03248492
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond
      or become resistant to current treatment. DS-8201a is a new experimental product that is a
      combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may
      slow down tumor growth. This might improve outcomes for these patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
primary purpose: Treatment
masking: None (Open Label)
masking description: In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
measure: Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
measure: Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.
measure: Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.
measure: Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.
measure: Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.
measure: Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
description: The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.
measure: Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
time frame: Baseline up to Week 6, 12, 18, 24, 30, 36 post dose
description: Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.
measure: Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)
time frame: Day 0 to Day 47 post last dose
description: TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.
arm group label: DS-8201a Low Dose
arm group type: Experimental
description: T-DM1 resistant/refractory (R/R) patients in the low dose treatment group
arm group label: DS-8201a Medium Dose
arm group type: Experimental
description: T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group
arm group label: DS-8201a High Dose
arm group type: Experimental
description: T-DM1 resistant/refractory (R/R) patients in the high dose treatment group
arm group label: Exploratory Arm
arm group type: Other
description: In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm
intervention type: Drug
intervention name: DS-8201a
description: DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.
arm group label: DS-8201a High Dose
arm group label: DS-8201a Low Dose
arm group label: DS-8201a Medium Dose
arm group label: Exploratory Arm
other name: Experimental product
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
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country: Belgium
country: Canada
country: France
country: Italy
country: Japan
country: Korea, Republic of
country: Spain
country: United Kingdom
country: United States
country: Germany
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Trastuzumab deruxtecan
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/
provided document: 
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reported events: 
certain agreements: 
point of contact: 