<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/NCT03023423</url>
  </required_header>
  <id_info>
    <org_study_id>CR108256</org_study_id>
    <secondary_id>2016-002579-83</secondary_id>
    <secondary_id>54767414LUC2001</secondary_id>
    <nct_id>NCT03023423</nct_id>
  </id_info>
  <brief_title>A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer</brief_title>
  <acronym>DARZALEX</acronym>
  <official_title>A Phase 1b/2, Open-Label, Randomized Study of Daratumumab Administered in Combination With Atezolizumab Compared With Atezolizumab Alone in Subjects With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung&#xD;
      cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus&#xD;
      atezolizumab alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized (study medication assigned to participants by chance), multicenter study will&#xD;
      provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with&#xD;
      previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety.&#xD;
      Participants who receive atezolizumab treatment with confirmed disease progression based on&#xD;
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to&#xD;
      treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is&#xD;
      expected that 100 participants will enroll in the study including 6 participants in the&#xD;
      safety run in phase. Data Monitoring Committee (DMC) will review ongoing data, and may&#xD;
      formulate recommendations on study conduct, including expansion of enrollment of some PD-L1&#xD;
      subgroups, resulting in greater than 96 participants. The participants in the safety run in&#xD;
      phase will be administered the combination of daratumumab and atezolizumab to determine the&#xD;
      safety and tolerability that will be evaluated by the Safety Evaluation Team (SET) for dose&#xD;
      limiting toxicity before the random assignment of participants in a 1:1 ratio in 2 treatment&#xD;
      arms. The study consists of 3 phases: Screening Phase (up to 28 days), Treatment Phase and&#xD;
      Post-Treatment Follow-up Phase which will continue until death, lost to follow-up, withdrawal&#xD;
      of consent, or the End of the Study [the study end is approximately 6 to 12 months after that&#xD;
      last participant is enrolled]. Participants will undergo tumor assessments (RECIST 1.1),&#xD;
      immunogenicity, pharmacokinetics, biomarkers and safety evaluations (adverse events,&#xD;
      laboratory tests, electrocardiogram [ECGs], vital sign measurements, physical examinations,&#xD;
      Eastern Cooperative Oncology Group [ECOG] performance status score) over the time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 23, 2016</start_date>
  <completion_date type="Actual">September 26, 2019</completion_date>
  <primary_completion_date type="Actual">May 17, 2018</primary_completion_date>
  <phase>Phase 1/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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Overall Response Rate (ORR)</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than [&lt;]10 millimeter [mm] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (&gt;=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and in 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, AEs after initiation of cross-over treatment were summarized separately in the crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>Duration of response was defined as duration from date of initial documentation of disease response to date of first objectively documented evidence of recurrence or progressive disease (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>Clinical benefit rate was defined as percentage of participants who achieved disease control (CR, PR, or SD). RECIST 1.1 Criteria for CR: Disappearance of all target lesions; all lymph nodes of non-pathological in size (&lt;10 mm short axis); normalization of tumor marker level. Criteria for PR: &gt;=30 % decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Criteria for SD: &lt;30% decrease in sum of diameters of all target lesions compared with baseline and &lt;20% increase compared with nadir, in absence of new lesions or unequivocal progression of nontarget lesions. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>PFS was defined as the duration from the date of randomization until the first documented disease progression (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daratumumab Serum Concentration</measure>
    <time_frame>Cycle 1 Day 1 (C1D1):predose and postdose; C2D1 and C3D1:predose; C3D15: predose and postdose; C4D1: predose and postdose; C8D1: predose and postdose; C12D1: predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)</time_frame>
    <description>Daratumumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atezolizumab Serum Concentration</measure>
    <time_frame>C1D1:predose and postdose; C1D2:predose and postdose; C2D1, C3D1:predose; C3D15:predose and postdose; C4D1:predose and postdose; C8D1:predose and postdose; C12D1:predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)</time_frame>
    <description>Atezolizumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Daratumumab Antibodies</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>Number of participants with antibodies to daratumumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Atezolizumab Antibodies</measure>
    <time_frame>Up to 1.5 years</time_frame>
    <description>Number of participants with antibodies to atezolizumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Treatment Arm A: Atezolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in Treatment Arm A will receive Atezolizumab 1,200 milligram (mg) intravenously (IV) on Day 1 of every 21-day cycle. Participants with confirmed disease progression based on RECIST 1.1 may cross over to Arm B and receive daratumumab and atezolizumab, provided crossover eligibility criteria are met.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Arm B: Atezolizumab and Daratumumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Participants will receive atezolizumab 1200 mg intravenously.</description>
    <arm_group_label>Treatment Arm A: Atezolizumab</arm_group_label>
    <arm_group_label>Treatment Arm B: Atezolizumab and Daratumumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Participants will receive daratumumab 16 mg/kg intravenously.</description>
    <arm_group_label>Treatment Arm B: Atezolizumab and Daratumumab</arm_group_label>
    <other_name>JNJ-54767414</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Have histologically or cytologically confirmed advanced or metastatic non-small cell&#xD;
             lung cancer (NSCLC) (Stage IIIb or greater)&#xD;
&#xD;
          -  Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) 1.1&#xD;
&#xD;
          -  Tumor cell programmed death-ligand 1 (PD-L1) score of tumor cells (TC)1-3 and immune&#xD;
             cell PD-L1 score of tumor-infiltrating immune cells (IC)0-3 as determined by an&#xD;
             immunohistochemistry (IHC) assay performed by the central laboratory on tissue&#xD;
             obtained after the last line of therapy&#xD;
&#xD;
          -  A woman of childbearing potential must have a negative highly sensitive serum&#xD;
             (beta-human chorionic gonadotropin [beta- hCG]) at Screening within 14 days prior to&#xD;
             study drug administration&#xD;
&#xD;
        Inclusion Criteria for Crossover:&#xD;
&#xD;
          -  Participants must have been randomized to Arm A of the study and had radiographic&#xD;
             disease progression according to RECIST 1.1&#xD;
&#xD;
          -  Participants must have a mandatory biopsy at the time of disease progression according&#xD;
             to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with&#xD;
             Sponsor is required&#xD;
&#xD;
          -  The first dose of atezolizumab in the crossover arm should be within 42 days of last&#xD;
             dose but no less than 21 days from the last dose prior to crossing over&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received any of the following prescribed medications or therapies in the past:&#xD;
&#xD;
               1. Anti-cluster of differentiation(CD)38 therapy, including daratumumab&#xD;
&#xD;
               2. CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4,&#xD;
                  anti-PD-1, and anti-PD-L1 therapies&#xD;
&#xD;
          -  Known to be seropositive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Prior allogeneic bone marrow transplantation or solid organ transplant&#xD;
&#xD;
          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies or fusion proteins&#xD;
&#xD;
          -  Active hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]&#xD;
             or prior history of hepatitis B, defined by presence of antibodies to hepatitis B core&#xD;
             antigen [anti-HBc], regardless of hepatitis B surface antibody [anti-HBs] status;&#xD;
             active hepatitis C or prior history of hepatitis C (anti-HCV positive), except in the&#xD;
             setting of a sustained virologic response (SVR), defined as aviremia 12 weeks after&#xD;
             completion of antiviral therapy. If hepatitis C virus (HCV) antibodies are detected,&#xD;
             an HCV RNA test for viral load by polymerase chain reaction (PCR) should be performed&#xD;
             at least 12 weeks after completion of antiviral therapy to rule out active infection&#xD;
&#xD;
        Exclusion Criteria for Crossover:&#xD;
&#xD;
          -  Received any subsequent anti-cancer therapies from the time between the last dose of&#xD;
             atezolizumab prior to the first administration of study drug after crossing over&#xD;
&#xD;
          -  Whole brain radiation within 28 days or other radiotherapy within 14 days prior to&#xD;
             first administration of study drug after crossing over&#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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boulogne Billancourt</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Caen Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Creteil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Haut-Rhin</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rennes cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Suresnes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Szekesfehervar</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tatabanya</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Otwock</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wieliszew</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Elche</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jaén</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leganés</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Murcia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Málaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palma de Mallorca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pozuelo de Alarcón</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Sebastián</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sótano</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <results_first_submitted>May 17, 2019</results_first_submitted>
  <results_first_submitted_qc>July 3, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 23, 2019</results_first_posted>
  <last_update_submitted>November 5, 2019</last_update_submitted>
  <last_update_submitted_qc>November 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03023423/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03023423/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 100 participants were enrolled in the study (7 in phase 1b [safety run-in phase], and 93 in Phase 2 [randomized phase]). Among them, 99 participants (7 in phase 1b [safety run-in phase], and 92 in phase 2 [randomized phase]) were randomized as 1 participant was randomized after the clinical cutoff date (17-May-2018).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Safety Run-in Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="P2">
          <title>Randomized Phase: Atezolizumab</title>
          <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="P3">
          <title>Randomized Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="46"/>
                <participants group_id="P3" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Crossover From Atezo to Dara + Atezo</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8">Participants who met crossover eligibility criteria entered to Dara + Atezo arm.</participants>
                <participants group_id="P3" count="0"/>
              </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_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="46"/>
                <participants group_id="P3" count="46"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Safety Run-in Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="B2">
          <title>Randomized Phase: Atezolizumab</title>
          <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="B3">
          <title>Randomized Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="46"/>
            <count group_id="B3" value="46"/>
            <count group_id="B4" value="99"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" spread="9.73"/>
                    <measurement group_id="B2" value="61.7" spread="10.05"/>
                    <measurement group_id="B3" value="63.2" spread="10.76"/>
                    <measurement group_id="B4" value="62.3" spread="10.29"/>
                  </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="3"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="38"/>
                    <measurement group_id="B4" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="41"/>
                    <measurement group_id="B4" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Non-Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>FRANCE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HUNGARY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPAIN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time from initial diagnosis</title>
          <description>Time from initial diagnosis is defined as the time from the initial diagnosis of non-small cell lung cancer (NSCLC) to the first dosing date or randomization date (if first dosing date is missing).</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.3" spread="9.29"/>
                    <measurement group_id="B2" value="18.8" spread="20.89"/>
                    <measurement group_id="B3" value="17.6" spread="14.17"/>
                    <measurement group_id="B4" value="17.6" spread="17.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>ECOG performance status was used to evaluate the effect of the disease status on the activities of daily living. ECOG performance status was determined by ECOG 5-point scale: 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all self-care, 3=Capable of limited self-care, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no self-care, totally confined to bed or chair, 5=Dead.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>ECOG Score 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG Score 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG Score 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Overall Response Rate (ORR)</title>
        <description>ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than [&lt;]10 millimeter [mm] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (&gt;=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>Intent-to-treat (ITT) analysis set included all participants who had entered the Randomized phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Overall Response Rate (ORR)</title>
          <description>ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than [&lt;]10 millimeter [mm] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (&gt;=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.</description>
          <population>Intent-to-treat (ITT) analysis set included all participants who had entered the Randomized phase of the study.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" lower_limit="4.9" upper_limit="26.3"/>
                    <measurement group_id="O2" value="4.3" lower_limit="0.5" upper_limit="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.03</ci_lower_limit>
            <ci_upper_limit>1.92</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and in 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, AEs after initiation of cross-over treatment were summarized separately in the crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>Safety analysis set included all participants who had received at least 1 administration of any study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Safety Run-in: Atezolizumab + Daratumumab</title>
            <description>Participants received daratumumab 16 milligram per kilogram (mg/kg) Intravenously (IV) weekly for first 3 cycles and every 3 weeks for all cycles thereafter along with atezolizumab IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O4">
            <title>Randomized Phase: Atezo Crossed Over to Dara + Atezo</title>
            <description>Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and in 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, AEs after initiation of cross-over treatment were summarized separately in the crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.</description>
          <population>Safety analysis set included all participants who had received at least 1 administration of any study medication.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="44"/>
                <count group_id="O4" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="42"/>
                    <measurement group_id="O3" value="44"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DoR)</title>
        <description>Duration of response was defined as duration from date of initial documentation of disease response to date of first objectively documented evidence of recurrence or progressive disease (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>ITT analysis set included all participants who had entered the Randomized phase of the study. Here, N (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DoR)</title>
          <description>Duration of response was defined as duration from date of initial documentation of disease response to date of first objectively documented evidence of recurrence or progressive disease (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>ITT analysis set included all participants who had entered the Randomized phase of the study. Here, N (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.</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="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" lower_limit="2.2" upper_limit="5.8"/>
                    <measurement group_id="O2" value="2.9" lower_limit="NA" upper_limit="NA">Here NA signifies that the lower and upper limit of 95% Confidence Interval (CI) were not estimable due to lesser number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate</title>
        <description>Clinical benefit rate was defined as percentage of participants who achieved disease control (CR, PR, or SD). RECIST 1.1 Criteria for CR: Disappearance of all target lesions; all lymph nodes of non-pathological in size (&lt;10 mm short axis); normalization of tumor marker level. Criteria for PR: &gt;=30 % decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Criteria for SD: &lt;30% decrease in sum of diameters of all target lesions compared with baseline and &lt;20% increase compared with nadir, in absence of new lesions or unequivocal progression of nontarget lesions. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate</title>
          <description>Clinical benefit rate was defined as percentage of participants who achieved disease control (CR, PR, or SD). RECIST 1.1 Criteria for CR: Disappearance of all target lesions; all lymph nodes of non-pathological in size (&lt;10 mm short axis); normalization of tumor marker level. Criteria for PR: &gt;=30 % decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Criteria for SD: &lt;30% decrease in sum of diameters of all target lesions compared with baseline and &lt;20% increase compared with nadir, in absence of new lesions or unequivocal progression of nontarget lesions. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.5" lower_limit="28.9" upper_limit="58.9"/>
                    <measurement group_id="O2" value="52.2" lower_limit="36.9" upper_limit="67.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS)</title>
        <description>PFS was defined as the duration from the date of randomization until the first documented disease progression (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS)</title>
          <description>PFS was defined as the duration from the date of randomization until the first documented disease progression (PD) or death, whichever occurred first. PD: Sum of diameters increased by &gt;=20% and &gt;=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for &quot;unequivocal progression&quot; based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for &quot;unequivocal progression&quot; of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</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="46"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.48" lower_limit="1.38" upper_limit="2.76"/>
                    <measurement group_id="O2" value="1.68" lower_limit="1.41" upper_limit="2.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>ITT analysis set included all participants who had entered the Randomized phase of the study.</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="46"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="7.43" upper_limit="NA">Here NA signifies that the median and upper limit of 95% CI were not estimable due to lesser number of events.</measurement>
                    <measurement group_id="O2" value="7.13" lower_limit="3.52" upper_limit="NA">Here NA signifies that the upper limit of 95% CI was not estimable due to lesser number of events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daratumumab Serum Concentration</title>
        <description>Daratumumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Cycle 1 Day 1 (C1D1):predose and postdose; C2D1 and C3D1:predose; C3D15: predose and postdose; C4D1: predose and postdose; C8D1: predose and postdose; C12D1: predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)</time_frame>
        <population>Pharmacokinetic (PK)-evaluable analysis set included all participants who had received at least 1 dose of daratumumab or atezolizumab and had at least 1 postinfusion sample collected. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Safety Run-in: Atezolizumab + Daratumumab</title>
            <description>Participants received daratumumab 16 milligram per kilogram (mg/kg) Intravenously (IV) weekly for first 3 cycles and every 3 weeks for all cycles thereafter along with atezolizumab IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Daratumumab Serum Concentration</title>
          <description>Daratumumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>Pharmacokinetic (PK)-evaluable analysis set included all participants who had received at least 1 dose of daratumumab or atezolizumab and had at least 1 postinfusion sample collected. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.</population>
          <units>Microgram per milliliter (mcg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                    <measurement group_id="O2" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="417.13" spread="141.626"/>
                    <measurement group_id="O2" value="296.12" spread="85.660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="393.95" spread="139.480"/>
                    <measurement group_id="O2" value="278.42" spread="89.340"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="740.17" spread="99.515"/>
                    <measurement group_id="O2" value="487.65" spread="124.935"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 15 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="843.22" spread="156.792"/>
                    <measurement group_id="O2" value="552.79" spread="180.549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 15 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1088.73" spread="282.349"/>
                    <measurement group_id="O2" value="827.72" spread="266.085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="899.90" spread="123.305"/>
                    <measurement group_id="O2" value="574.81" spread="181.193"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1416.40" spread="353.415"/>
                    <measurement group_id="O2" value="856.30" spread="244.698"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 8 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="254.87" spread="NA">Here NA signifies that Standard Deviation could not be calculated for a single participant.</measurement>
                    <measurement group_id="O2" value="288.84" spread="177.187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 8 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="824.64" spread="NA">Here NA signifies that Standard Deviation could not be calculated for a single participant.</measurement>
                    <measurement group_id="O2" value="617.21" spread="239.962"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 12 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="260.21" spread="17.163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="405.14" spread="242.189"/>
                    <measurement group_id="O2" value="187.75" spread="110.531"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Last Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.84" spread="23.082"/>
                    <measurement group_id="O2" value="112.63" spread="115.727"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Atezolizumab Serum Concentration</title>
        <description>Atezolizumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>C1D1:predose and postdose; C1D2:predose and postdose; C2D1, C3D1:predose; C3D15:predose and postdose; C4D1:predose and postdose; C8D1:predose and postdose; C12D1:predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)</time_frame>
        <population>PK-evaluable analysis set: all participants who received at least 1 dose of daratumumab/atezolizumab and had at least 1 postinfusion sample collected. Here N (number of participants analyzed): participants evaluable for this outcome measure, and n (number of participants analyzed): participants evaluable for this outcome measure at given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Safety Run-in: Atezolizumab + Daratumumab</title>
            <description>Participants received daratumumab 16 milligram per kilogram (mg/kg) Intravenously (IV) weekly for first 3 cycles and every 3 weeks for all cycles thereafter along with atezolizumab IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Atezolizumab Serum Concentration</title>
          <description>Atezolizumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>PK-evaluable analysis set: all participants who received at least 1 dose of daratumumab/atezolizumab and had at least 1 postinfusion sample collected. Here N (number of participants analyzed): participants evaluable for this outcome measure, and n (number of participants analyzed): participants evaluable for this outcome measure at given timepoint.</population>
          <units>Microgram per milliliter (mcg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="37"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0.00" spread="0.000"/>
                    <measurement group_id="O3" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="37"/>
                    <count group_id="O3" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="396.51" spread="103.196"/>
                    <measurement group_id="O3" value="440.00" spread="93.145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 2 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                    <measurement group_id="O3" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 2 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="362.14" spread="43.434"/>
                    <measurement group_id="O3" value="343.82" spread="135.476"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="30"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.16" spread="15.305"/>
                    <measurement group_id="O2" value="78.85" spread="30.575"/>
                    <measurement group_id="O3" value="81.90" spread="20.021"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="21"/>
                    <count group_id="O3" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="176.50" spread="33.234"/>
                    <measurement group_id="O2" value="117.61" spread="33.227"/>
                    <measurement group_id="O3" value="123.51" spread="31.882"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="166.50" spread="37.477"/>
                    <measurement group_id="O2" value="145.64" spread="37.323"/>
                    <measurement group_id="O3" value="157.79" spread="37.819"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="612.25" spread="81.578"/>
                    <measurement group_id="O2" value="539.24" spread="116.291"/>
                    <measurement group_id="O3" value="482.33" spread="139.879"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 8 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="158.23" spread="77.778"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 8 Day 1 Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="527.50" spread="213.492"/>
                    <measurement group_id="O3" value="515.25" spread="214.177"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 12 Day 1 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="1"/>
                    <count group_id="O3" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="183.00" spread="NA">Here NA signifies that the standard deviation could not be calculated for a single participant.</measurement>
                    <measurement group_id="O3" value="248.00" spread="NA">Here NA signifies that the standard deviation could not be calculated for a single participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="136.43" spread="73.002"/>
                    <measurement group_id="O2" value="129.55" spread="79.720"/>
                    <measurement group_id="O3" value="141.62" spread="71.756"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Last Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.10" spread="NA">Here NA signifies that the standard deviation could not be calculated for a single participant.</measurement>
                    <measurement group_id="O2" value="13.17" spread="8.386"/>
                    <measurement group_id="O3" value="115.10" spread="146.937"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-Daratumumab Antibodies</title>
        <description>Number of participants with antibodies to daratumumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>The immunogenicity-evaluable analysis set included all participants who received at least 1 dose of atezolizumab or daratumumab and had appropriate samples for detection of antibodies to atezolizumab or daratumumab. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Safety Run-in: Atezolizumab + Daratumumab</title>
            <description>Participants received daratumumab 16 milligram per kilogram (mg/kg) Intravenously (IV) weekly for first 3 cycles and every 3 weeks for all cycles thereafter along with atezolizumab IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Daratumumab Antibodies</title>
          <description>Number of participants with antibodies to daratumumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>The immunogenicity-evaluable analysis set included all participants who received at least 1 dose of atezolizumab or daratumumab and had appropriate samples for detection of antibodies to atezolizumab or daratumumab. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-Atezolizumab Antibodies</title>
        <description>Number of participants with antibodies to atezolizumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
        <time_frame>Up to 1.5 years</time_frame>
        <population>The immunogenicity-evaluable analysis set included all participants who received at least 1 dose of atezolizumab or daratumumab and had appropriate samples for detection of antibodies to atezolizumab or daratumumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Safety Run-in: Atezolizumab + Daratumumab</title>
            <description>Participants received daratumumab 16 milligram per kilogram (mg/kg) Intravenously (IV) weekly for first 3 cycles and every 3 weeks for all cycles thereafter along with atezolizumab IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Phase: Atezolizumab</title>
            <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Phase: Daratumumab + Atezolizumab</title>
            <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Atezolizumab Antibodies</title>
          <description>Number of participants with antibodies to atezolizumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.</description>
          <population>The immunogenicity-evaluable analysis set included all participants who received at least 1 dose of atezolizumab or daratumumab and had appropriate samples for detection of antibodies to atezolizumab or daratumumab.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 1.5 years</time_frame>
      <desc>Safety analysis set included participants who received at least 1 administration of any study medication. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, adverse events (AEs) after initiation of cross-over treatment summarized separately in crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.</desc>
      <group_list>
        <group group_id="E1">
          <title>Safety Run-in Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="E2">
          <title>Randomized Phase: Atezolizumab</title>
          <description>Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="E3">
          <title>Randomized Phase: Daratumumab + Atezolizumab</title>
          <description>Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
        <group group_id="E4">
          <title>Randomized Phase: Atezo Crossed Over to Dara + Atezo</title>
          <description>Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Cardiac Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Cardio-Respiratory Arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rectal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General Physical Health Deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sudden Death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oral Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Superinfection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Transient Ischaemic Attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vocal Cord Paralysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchial Fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Bronchial Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Painful Respiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Version 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="41" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Deficiency Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Ventricular Extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sinus Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Eye Irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Visual Acuity Reduced</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Chest Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>General Physical Health Deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypothermia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Localised Oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Mucosal Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Secretion Discharge</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Temperature Intolerance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Drug Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oral Herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Tooth Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Buttock Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood Lactate Dehydrogenase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Eastern Cooperative Oncology Group Performance Status Worsened</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gamma-Glutamyltransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lipase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oxygen Saturation Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Weight Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </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="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Groin Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Muscle Contracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Spinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypokinesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sleep Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Bladder Spasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Renal Colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Renal Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Gynaecomastia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry Throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Throat Irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dyspnoea Exertional</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Laryngeal Oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Throat Tightness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Upper-Airway Cough Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dermatitis Acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hair Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Night Sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash Papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash Pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Skin Lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Venous Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </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>A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Executive Medical Director</name_or_title>
      <organization>Janssen Research &amp; Development, LLC</organization>
      <phone>844-434-4210</phone>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT03023423
org study id: CR108256
secondary id: 2016-002579-83
secondary id: 54767414LUC2001
nct id: NCT03023423
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated device: No
The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung
      cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus
      atezolizumab alone.
This randomized (study medication assigned to participants by chance), multicenter study will
      provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with
      previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety.
      Participants who receive atezolizumab treatment with confirmed disease progression based on
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to
      treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is
      expected that 100 participants will enroll in the study including 6 participants in the
      safety run in phase. Data Monitoring Committee (DMC) will review ongoing data, and may
      formulate recommendations on study conduct, including expansion of enrollment of some PD-L1
      subgroups, resulting in greater than 96 participants. The participants in the safety run in
      phase will be administered the combination of daratumumab and atezolizumab to determine the
      safety and tolerability that will be evaluated by the Safety Evaluation Team (SET) for dose
      limiting toxicity before the random assignment of participants in a 1:1 ratio in 2 treatment
      arms. The study consists of 3 phases: Screening Phase (up to 28 days), Treatment Phase and
      Post-Treatment Follow-up Phase which will continue until death, lost to follow-up, withdrawal
      of consent, or the End of the Study [the study end is approximately 6 to 12 months after that
      last participant is enrolled]. Participants will undergo tumor assessments (RECIST 1.1),
      immunogenicity, pharmacokinetics, biomarkers and safety evaluations (adverse events,
      laboratory tests, electrocardiogram [ECGs], vital sign measurements, physical examinations,
      Eastern Cooperative Oncology Group [ECOG] performance status score) over the time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Overall Response Rate (ORR)
time frame: Up to 1.5 years
description: ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than [<]10 millimeter [mm] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (>=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.
measure: Number of Participants With Adverse Events
time frame: Up to 1.5 years
description: An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and in 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, AEs after initiation of cross-over treatment were summarized separately in the crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.
measure: Duration of Response (DoR)
time frame: Up to 1.5 years
description: Duration of response was defined as duration from date of initial documentation of disease response to date of first objectively documented evidence of recurrence or progressive disease (PD) or death, whichever occurred first. PD: Sum of diameters increased by >=20% and >=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Clinical Benefit Rate
time frame: Up to 1.5 years
description: Clinical benefit rate was defined as percentage of participants who achieved disease control (CR, PR, or SD). RECIST 1.1 Criteria for CR: Disappearance of all target lesions; all lymph nodes of non-pathological in size (<10 mm short axis); normalization of tumor marker level. Criteria for PR: >=30 % decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Criteria for SD: <30% decrease in sum of diameters of all target lesions compared with baseline and <20% increase compared with nadir, in absence of new lesions or unequivocal progression of nontarget lesions. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Progression-Free Survival (PFS)
time frame: Up to 1.5 years
description: PFS was defined as the duration from the date of randomization until the first documented disease progression (PD) or death, whichever occurred first. PD: Sum of diameters increased by >=20% and >=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease [SD]/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Overall Survival (OS)
time frame: Up to 1.5 years
description: Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Daratumumab Serum Concentration
time frame: Cycle 1 Day 1 (C1D1):predose and postdose; C2D1 and C3D1:predose; C3D15: predose and postdose; C4D1: predose and postdose; C8D1: predose and postdose; C12D1: predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)
description: Daratumumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Atezolizumab Serum Concentration
time frame: C1D1:predose and postdose; C1D2:predose and postdose; C2D1, C3D1:predose; C3D15:predose and postdose; C4D1:predose and postdose; C8D1:predose and postdose; C12D1:predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)
description: Atezolizumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Number of Participants With Anti-Daratumumab Antibodies
time frame: Up to 1.5 years
description: Number of participants with antibodies to daratumumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
measure: Number of Participants With Anti-Atezolizumab Antibodies
time frame: Up to 1.5 years
description: Number of participants with antibodies to atezolizumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.
arm group label: Treatment Arm A: Atezolizumab
arm group type: Experimental
description: Participants in Treatment Arm A will receive Atezolizumab 1,200 milligram (mg) intravenously (IV) on Day 1 of every 21-day cycle. Participants with confirmed disease progression based on RECIST 1.1 may cross over to Arm B and receive daratumumab and atezolizumab, provided crossover eligibility criteria are met.
arm group label: Treatment Arm B: Atezolizumab and Daratumumab
arm group type: Experimental
description: Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
intervention type: Drug
intervention name: Atezolizumab
description: Participants will receive atezolizumab 1200 mg intravenously.
arm group label: Treatment Arm A: Atezolizumab
arm group label: Treatment Arm B: Atezolizumab and Daratumumab
intervention type: Drug
intervention name: Daratumumab
description: Participants will receive daratumumab 16 mg/kg intravenously.
arm group label: Treatment Arm B: Atezolizumab and Daratumumab
other name: JNJ-54767414
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
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country: France
country: Hungary
country: Poland
country: Spain
country: United States
country: Germany
country: Russian Federation
country: United Kingdom
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Atezolizumab
mesh term: Daratumumab
provided document: 
provided document: 
participant flow: 
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reported events: 
certain agreements: 
point of contact: 