<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/NCT02256436</url>
  </required_header>
  <id_info>
    <org_study_id>3475-045</org_study_id>
    <secondary_id>2014-002009-40</secondary_id>
    <secondary_id>152903</secondary_id>
    <secondary_id>MK-3475-045</secondary_id>
    <nct_id>NCT02256436</nct_id>
  </id_info>
  <brief_title>A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)</brief_title>
  <official_title>A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants with metastatic or locally advanced/unresectable urothelial cancer that has&#xD;
      recurred or progressed following platinum-based chemotherapy will be randomly assigned to&#xD;
      receive Investigator's choice of paclitaxel, docetaxel, or vinflunine (Control), or&#xD;
      pembrolizumab. The primary study hypotheses are that pembrolizumab will prolong Overall&#xD;
      Survival (OS) and Progression-free Survival (PFS) compared to paclitaxel, docetaxel, or&#xD;
      vinflunine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the purposes of this study, participants with a programmed cell death-ligand 1 (PD-L1)&#xD;
      combined positive score (CPS) ≥10% were considered to have a strongly PD-L1 positive tumor&#xD;
      status and participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor&#xD;
      status.&#xD;
&#xD;
      Effective with Amendment 15, eligible participants who are allocated to the Control arm&#xD;
      (Investigator's Choice) and experience disease progression will be provided with the&#xD;
      opportunity to switch over to receive pembrolizumab 200 mg one time every three weeks (Q3W)&#xD;
      for up to two years of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2014</start_date>
  <completion_date type="Actual">October 1, 2020</completion_date>
  <primary_completion_date type="Actual">September 7, 2016</primary_completion_date>
  <phase>Phase 3</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>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS) - All Participants</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS - Participants With PD-L1 Positive Tumors</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced an Adverse Event (AE)</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was reported for each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinued Study Treatment Due to an AE</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per RECIST 1.1 - All Participants</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per mRECIST - Participants With PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per mRECIST - All Participants</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in all randomized participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per mRECIST - Participants With PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per mRECIST - All Participants</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR Per RECIST 1.1 - All Participants</measure>
    <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
    <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants based on BICR and was analyzed using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">542</enrollment>
  <condition>Urothelial Cancer</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experience disease progression may be able to switch over to receive pembrolizumab 200 mg Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to approximately 1 additional year).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vinflunine</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>docetaxel</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the renal&#xD;
             pelvis, ureter, bladder, or urethra, that is transitional cell or mixed&#xD;
             transitional/non-transitional (predominantly transitional) cell type&#xD;
&#xD;
          -  Progression or recurrence of urothelial cancer following a first-line&#xD;
             platinum-containing regimen (e.g cisplatin, carboplatin) for metastatic or inoperable&#xD;
             locally advanced disease; or adjuvant platinum-based therapy following cystectomy for&#xD;
             localized muscle-invasive urothelial cancer with recurrence/progression &lt;=12 months&#xD;
             following completion of therapy; or neoadjuvant platinum-containing therapy prior to&#xD;
             cystectomy for localized muscle-invasive urothelial cancer with recurrence &lt;=12 months&#xD;
             following completion of therapy&#xD;
&#xD;
          -  No more than 2 prior lines of systemic chemotherapy for metastatic urothelial cancer&#xD;
&#xD;
          -  Able to provide tissue for biomarker analysis from an archival tissue sample or newly&#xD;
             obtained core or excisional biopsy of a tumor lesion not previously irradiated&#xD;
&#xD;
          -  Measureable disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Female participants of childbearing potential have a negative urine or serum pregnancy&#xD;
             test; or are surgically sterile, or willing to use 2 acceptable methods of birth&#xD;
             control, or abstain from heterosexual activity for the course of the study through 120&#xD;
             days after the last dose of pembrolizumab or 180 days after the last dose of&#xD;
             paclitaxel, docetaxel, or vinflunine&#xD;
&#xD;
          -  Male participants must be willing to use an adequate method of contraception starting&#xD;
             with the first dose of study medication through 120 days after the last dose of&#xD;
             pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Urothelial cancer that is suitable for local therapy administered with curative intent&#xD;
&#xD;
          -  Currently participating in or has participated in a study of an investigational agent&#xD;
             or using an investigational device within 4 weeks prior to the first dose of trial&#xD;
             medication&#xD;
&#xD;
          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form&#xD;
             of immunosuppressive therapy within 7 days prior to the first dose of study medication&#xD;
&#xD;
          -  Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not&#xD;
             recovered from adverse events due to agents administered more than 4 weeks earlier&#xD;
&#xD;
          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2&#xD;
             weeks of study Day 1 or not recovered from adverse events due to a previously&#xD;
             administered agent&#xD;
&#xD;
          -  Prior therapy with all choices of active comparator&#xD;
&#xD;
          -  Known additional malignancy that is progressing or requires active treatment with the&#xD;
             exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin&#xD;
             that has undergone potentially curative therapy or in situ cancer; or prostate cancer&#xD;
             that was identified incidentally following cystoprostatectomy for bladder cancer that&#xD;
             is Stage T2N0M0 or lower, Gleason score&lt;= 6, or prostatic-specific antigen (PSA)&#xD;
             undetectable&#xD;
&#xD;
          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Active autoimmune disease requiring systemic treatment within the past 3 months or a&#xD;
             documented history of clinically severe autoimmune disease, or a syndrome that&#xD;
             requires systemic or immunosuppressive agents&#xD;
&#xD;
          -  Active cardiac disease&#xD;
&#xD;
          -  Evidence of interstitial lung disease or active non-infectious pneumonitis&#xD;
&#xD;
          -  Active infection requiring systemic therapy&#xD;
&#xD;
          -  History of severe hypersensitivity reaction to paclitaxel, docetaxel, or to other&#xD;
             drugs formulated with polysorbate 80 or polyoxyethylated castor oil, or to vinflunine&#xD;
             or other vinca alkaloids&#xD;
&#xD;
          -  Requires ongoing therapy with a medication that is a strong inhibitor or inducer of&#xD;
             the cytochrome 3A4 (CYP3A4) enzymes&#xD;
&#xD;
          -  Pregnant, breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the screening visit through 120 days&#xD;
             after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel,&#xD;
             docetaxel, or vinflunine&#xD;
&#xD;
          -  Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent,&#xD;
             or with an agent directed to another co-inhibitory T-cell receptor&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Active hepatitis B or hepatitis C&#xD;
&#xD;
          -  Received a live virus vaccine within 30 days of planned start of trial treatment&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Norway</country>
    <country>Peru</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Puerto Rico</country>
    <country>Romania</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical trials Information</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <results_first_submitted>June 12, 2017</results_first_submitted>
  <results_first_submitted_qc>July 28, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 31, 2017</results_first_posted>
  <last_update_submitted>August 23, 2021</last_update_submitted>
  <last_update_submitted_qc>August 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Programmed Cell Death-1 (PD1, PD-1)</keyword>
  <keyword>Programmed Death-Ligand 1 (PDL1, PD-L1)</keyword>
  <keyword>Bladder cancer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02256436/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Per protocol, 13 participants randomized to receive Control were switched over to receive Pembrolizumab. Per protocol, response/progression or adverse events that occurred during a non-randomized switch-over or second course of pembrolizumab were not counted towards efficacy or safety outcome measures, respectively. These results are for randomized treatment only.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
        </group>
        <group group_id="P2">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="272"/>
                <participants group_id="P2" count="270"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="255"/>
                <participants group_id="P2" count="266"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Switched Over to Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="272"/>
                <participants group_id="P2" count="270"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="216"/>
                <participants group_id="P2" count="208"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Transferred to Extension Study</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did Not Continue on Extension Study</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control</title>
          <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
        </group>
        <group group_id="B2">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="272"/>
            <count group_id="B2" value="270"/>
            <count group_id="B3" value="542"/>
          </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="65.1" spread="9.2"/>
                    <measurement group_id="B2" value="66.0" spread="10.2"/>
                    <measurement group_id="B3" value="65.5" spread="9.7"/>
                  </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="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="202"/>
                    <measurement group_id="B2" value="200"/>
                    <measurement group_id="B3" value="402"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="272"/>
                <count group_id="O2" value="270"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" lower_limit="2.3" upper_limit="3.5"/>
                    <measurement group_id="O2" value="2.1" lower_limit="2.0" upper_limit="2.2"/>
                  </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>
            <groups_desc>PFS - All Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.41648</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.81</ci_lower_limit>
            <ci_upper_limit>1.19</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) - All Participants</title>
        <description>OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) - All Participants</title>
          <description>OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="272"/>
                <count group_id="O2" value="270"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="5.1" lower_limit="6.1" upper_limit="8.3"/>
                    <measurement group_id="O2" value="10.3" spread="37.8" lower_limit="8.0" upper_limit="11.8"/>
                  </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>
            <groups_desc>OS - All Participants (Note: ECOG PS=Eastern Cooperative Oncology Group Performance Status)</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00224</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.73</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.59</ci_lower_limit>
            <ci_upper_limit>0.91</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="120"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" lower_limit="2.2" upper_limit="3.4"/>
                    <measurement group_id="O2" value="2.1" lower_limit="2.0" upper_limit="2.4"/>
                  </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>
            <groups_desc>PFS - PD-L1 positive participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.26443</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.68</ci_lower_limit>
            <ci_upper_limit>1.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>OS - Participants With PD-L1 Positive Tumors</title>
        <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>OS - Participants With PD-L1 Positive Tumors</title>
          <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="120"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" lower_limit="4.7" upper_limit="8.8"/>
                    <measurement group_id="O2" value="11.3" lower_limit="7.7" upper_limit="16.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>OS - PD-L1 positive participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00239</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.61</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.43</ci_lower_limit>
            <ci_upper_limit>0.86</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="90"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" lower_limit="2.2" upper_limit="3.4"/>
                    <measurement group_id="O2" value="2.1" lower_limit="1.9" upper_limit="2.1"/>
                  </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>
            <groups_desc>PFS - Strongly PD-L1 positive participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.23958</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.89</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.61</ci_lower_limit>
            <ci_upper_limit>1.28</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>OS - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
        <time_frame>Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>OS - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="90"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" lower_limit="4.0" upper_limit="7.4"/>
                    <measurement group_id="O2" value="8.0" lower_limit="5.0" upper_limit="12.3"/>
                  </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>
            <groups_desc>OS - Strongly PD-L1 positive participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00483</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.57</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.37</ci_lower_limit>
            <ci_upper_limit>0.88</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced an Adverse Event (AE)</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was reported for each arm.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced an Adverse Event (AE)</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was reported for each arm.</description>
          <population>The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="255"/>
                <count group_id="O2" value="266"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="250"/>
                    <measurement group_id="O2" value="250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Discontinued Study Treatment Due to an AE</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Study Treatment Due to an AE</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm.</description>
          <population>The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="255"/>
                <count group_id="O2" value="266"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="90"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" lower_limit="2.5" upper_limit="13.9"/>
                    <measurement group_id="O2" value="20.3" lower_limit="11.8" upper_limit="31.2"/>
                  </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>
            <groups_desc>ORR per RECIST 1.1 - Strongly PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00061</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>17.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.8</ci_lower_limit>
            <ci_upper_limit>29.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</title>
        <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</title>
          <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="120"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" lower_limit="4.1" upper_limit="14.8"/>
                    <measurement group_id="O2" value="22.7" lower_limit="15.3" upper_limit="31.7"/>
                  </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>
            <groups_desc>ORR per RECIST 1.1 - PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00049</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>15.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.5</ci_lower_limit>
            <ci_upper_limit>25.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per RECIST 1.1 - All Participants</title>
        <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per RECIST 1.1 - All Participants</title>
          <description>ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="272"/>
                <count group_id="O2" value="270"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="7.6" upper_limit="15.4"/>
                    <measurement group_id="O2" value="21.1" lower_limit="16.4" upper_limit="26.5"/>
                  </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>
            <groups_desc>ORR per RECIST 1.1 - All Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00068</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>10.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.9</ci_lower_limit>
            <ci_upper_limit>16.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="90"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" lower_limit="2.4" upper_limit="3.7"/>
                    <measurement group_id="O2" value="2.1" lower_limit="2.0" upper_limit="3.7"/>
                  </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>
            <groups_desc>PFS per mRECIST - Strongly PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.07066</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.53</ci_lower_limit>
            <ci_upper_limit>1.11</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per mRECIST - Participants With PD-L1 Positive Tumors</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per mRECIST - Participants With PD-L1 Positive Tumors</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="120"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" lower_limit="2.6" upper_limit="3.6"/>
                    <measurement group_id="O2" value="2.1" lower_limit="2.0" upper_limit="3.7"/>
                  </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>
            <groups_desc>PFS per mRECIST - PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.08745</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.82</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.60</ci_lower_limit>
            <ci_upper_limit>1.10</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per mRECIST - All Participants</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in all randomized participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per mRECIST - All Participants</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in all randomized participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="272"/>
                <count group_id="O2" value="270"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" lower_limit="3.1" upper_limit="3.8"/>
                    <measurement group_id="O2" value="2.2" lower_limit="2.1" upper_limit="3.3"/>
                  </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>
            <groups_desc>PFS per mRECIST - All Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.05328</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Regression, Cox</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>1.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="90"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" lower_limit="3.2" upper_limit="15.4"/>
                    <measurement group_id="O2" value="24.3" lower_limit="15.1" upper_limit="35.7"/>
                  </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>
            <groups_desc>ORR per mRECIST - Strongly PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00009</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>21.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10.1</ci_lower_limit>
            <ci_upper_limit>34.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per mRECIST - Participants With PD-L1 Positive Tumors</title>
        <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per mRECIST - Participants With PD-L1 Positive Tumors</title>
          <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="120"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" lower_limit="4.7" upper_limit="15.8"/>
                    <measurement group_id="O2" value="28.2" lower_limit="20.0" upper_limit="37.6"/>
                  </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>
            <groups_desc>ORR per mRECIST - PD-L1 Positive Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00002</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>21.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>11.1</ci_lower_limit>
            <ci_upper_limit>31.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per mRECIST - All Participants</title>
        <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per mRECIST - All Participants</title>
          <description>ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.</description>
          <population>The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="272"/>
                <count group_id="O2" value="270"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" lower_limit="7.9" upper_limit="15.8"/>
                    <measurement group_id="O2" value="25.2" lower_limit="20.1" upper_limit="30.8"/>
                  </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>
            <groups_desc>ORR per mRECIST - All Participants</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.00001</p_value>
            <p_value_desc>One-sided p-value for testing H0: difference in %=0; H1: difference in %&gt;0</p_value_desc>
            <method>Miettinen &amp; Nurminen method</method>
            <method_desc>Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy</method_desc>
            <param_type>Difference in Percentages</param_type>
            <param_value>13.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>7.4</ci_lower_limit>
            <ci_upper_limit>20.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
        <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized strongly PD-L1 positive participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors</title>
          <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
          <population>The analysis population consisted of all randomized strongly PD-L1 positive participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" lower_limit="2.8" upper_limit="NA">NA= DOR upper 95% confidence limit was undefined because the DOR rate was not low enough at the time of the cut-off date.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="8.2" upper_limit="NA">NA= Median DOR was not reached because there were not enough events, DOR upper 95% confidence limit was undefined because the DOR rate was not low enough at the time of the cut-off date.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</title>
        <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized PD-L1 positive participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors</title>
          <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on BICR and was analyzed using the Kaplan-Meier method.</description>
          <population>The analysis population consisted of all randomized PD-L1 positive participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="10"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="2.8" upper_limit="NA">NA= Median DOR was not reached because there were not enough events, DOR upper 95% confidence limit was undefined because the DOR rate was not low enough at the time of the cut-off date.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="21.8" upper_limit="NA">NA= Median DOR was not reached because there were not enough events, DOR upper 95% confidence limit was undefined because the DOR rate was not low enough at the time of the cut-off date.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOR Per RECIST 1.1 - All Participants</title>
        <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants based on BICR and was analyzed using the Kaplan-Meier method.</description>
        <time_frame>Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)</time_frame>
        <population>The analysis population consisted of all randomized participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
          </group>
          <group group_id="O2">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
          </group>
        </group_list>
        <measure>
          <title>DOR Per RECIST 1.1 - All Participants</title>
          <description>For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants based on BICR and was analyzed using the Kaplan-Meier method.</description>
          <population>The analysis population consisted of all randomized participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.</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="30"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" lower_limit="4.0" upper_limit="20.3"/>
                    <measurement group_id="O2" value="NA" lower_limit="15.9" upper_limit="NA">NA = Median DOR was not reached because there were not enough events, DOR upper 95% confidence limit was undefined because the DOR rate was not low enough at the time of the cut-off date.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through end of trial analysis database cut-off date of 01-Oct-2020 (Up to approximately 71 months)</time_frame>
      <desc>All-Cause Mortality table includes all randomized participants. Serious and Other AEs include all treated participants according to treatment received. Per protocol, MedDRA preferred terms &quot;Neoplasm progression&quot;, &quot;Malignant neoplasm progression&quot; and &quot;Disease progression&quot; unrelated to drug excluded as AEs. Thirteen participants randomized to receive Control were switched over to pembrolizumab per protocol and were monitored for AEs separately.</desc>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Participants received paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experienced disease progression may have been able to switch over to receive pembrolizumab 200 mg IV Q3W for up to 35 treatment administrations (up to approximately 2 years).</description>
        </group>
        <group group_id="E2">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stopped pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab 200 mg IV Q3W for up to 17 cycles (up to approximately 1 additional year).</description>
        </group>
        <group group_id="E3">
          <title>Control Switched Over to Pembrolizumab</title>
          <description>Per protocol, participants originally randomized to the Control arm that experienced disease progression were switched over to receive pembrolizumab 200 mg IV on Day 1 Q3W.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="230" subjects_at_risk="272"/>
                <counts group_id="E2" subjects_affected="224" subjects_at_risk="270"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="104" subjects_at_risk="255"/>
                <counts group_id="E2" subjects_affected="107" subjects_at_risk="266"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="255"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Anaemia of malignant disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="16" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nephrogenic anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Normocytic anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia of malignancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Anal incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastrointestinal perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ileus paralytic</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Intestinal perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Intestinal pseudo-obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Large intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Retroperitoneal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Subileus</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyperthermia malignant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Catheter site infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fournier's gangrene</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pelvic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Post procedural infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Psoas abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="255"/>
                <counts group_id="E2" events="16" subjects_affected="12" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Incisional hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pelvic fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Stoma site haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bacterial test positive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blood calcium increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cachexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fluid retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Type 1 diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vitamin B1 deficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gouty arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Periostitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Prostate cancer recurrent</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urethral cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Posterior reversible encephalopathy syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Device malfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Device occlusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </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" events="6" subjects_affected="6" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Autoimmune nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bladder neck obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Prerenal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Renal injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Female genital tract fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pelvic fluid collection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypovolaemic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Iliac artery occlusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Superior vena cava syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vasoconstriction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="237" subjects_at_risk="255"/>
                <counts group_id="E2" subjects_affected="236" subjects_at_risk="266"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="139" subjects_affected="86" subjects_at_risk="255"/>
                <counts group_id="E2" events="61" subjects_affected="45" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="74" subjects_affected="41" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="24" subjects_affected="21" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="40" subjects_affected="33" subjects_at_risk="255"/>
                <counts group_id="E2" events="37" subjects_affected="32" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="255"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="105" subjects_affected="79" subjects_at_risk="255"/>
                <counts group_id="E2" events="63" subjects_affected="54" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="69" subjects_affected="47" subjects_at_risk="255"/>
                <counts group_id="E2" events="72" subjects_affected="43" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="100" subjects_affected="73" subjects_at_risk="255"/>
                <counts group_id="E2" events="62" subjects_affected="56" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="35" subjects_affected="23" subjects_at_risk="255"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="47" subjects_affected="34" subjects_at_risk="255"/>
                <counts group_id="E2" events="47" subjects_affected="38" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="67" subjects_affected="52" subjects_at_risk="255"/>
                <counts group_id="E2" events="36" subjects_affected="33" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="107" subjects_affected="85" subjects_at_risk="255"/>
                <counts group_id="E2" events="83" subjects_affected="66" subjects_at_risk="266"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="255"/>
                <counts group_id="E2" events="14" subjects_affected="10" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="24" subjects_affected="18" subjects_at_risk="255"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="48" subjects_affected="39" subjects_at_risk="255"/>
                <counts group_id="E2" events="36" subjects_affected="31" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="38" subjects_affected="30" subjects_at_risk="255"/>
                <counts group_id="E2" events="44" subjects_affected="36" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="23" subjects_affected="15" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="30" subjects_affected="27" subjects_at_risk="255"/>
                <counts group_id="E2" events="45" subjects_affected="33" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="15" subjects_affected="14" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="15" subjects_affected="14" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="16" subjects_affected="13" subjects_at_risk="255"/>
                <counts group_id="E2" events="22" subjects_affected="13" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="73" subjects_affected="40" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="23" subjects_affected="22" subjects_at_risk="255"/>
                <counts group_id="E2" events="30" subjects_affected="25" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="41" subjects_affected="22" subjects_at_risk="255"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="65" subjects_affected="53" subjects_at_risk="255"/>
                <counts group_id="E2" events="64" subjects_affected="57" subjects_at_risk="266"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="255"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="18" subjects_at_risk="255"/>
                <counts group_id="E2" events="20" subjects_affected="16" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="11" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="57" subjects_affected="31" subjects_at_risk="255"/>
                <counts group_id="E2" events="35" subjects_affected="30" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="22" subjects_affected="21" subjects_at_risk="255"/>
                <counts group_id="E2" events="47" subjects_affected="40" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="255"/>
                <counts group_id="E2" events="16" subjects_affected="15" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="17" subjects_at_risk="255"/>
                <counts group_id="E2" events="20" subjects_affected="17" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="31" subjects_affected="27" subjects_at_risk="255"/>
                <counts group_id="E2" events="28" subjects_affected="24" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Synovitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="26" subjects_affected="19" subjects_at_risk="255"/>
                <counts group_id="E2" events="22" subjects_affected="19" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="255"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="18" subjects_affected="14" subjects_at_risk="255"/>
                <counts group_id="E2" events="19" subjects_affected="14" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="43" subjects_affected="31" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="34" subjects_affected="28" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="255"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="255"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="255"/>
                <counts group_id="E2" events="22" subjects_affected="19" subjects_at_risk="266"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="21" subjects_affected="17" subjects_at_risk="255"/>
                <counts group_id="E2" events="43" subjects_affected="30" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="20" subjects_affected="18" subjects_at_risk="255"/>
                <counts group_id="E2" events="51" subjects_affected="39" subjects_at_risk="266"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="23" subjects_affected="23" subjects_at_risk="255"/>
                <counts group_id="E2" events="38" subjects_affected="31" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="255"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="12" subjects_affected="8" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="106" subjects_affected="100" subjects_at_risk="255"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="255"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="255"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="255"/>
                <counts group_id="E2" events="88" subjects_affected="66" subjects_at_risk="266"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="19" subjects_affected="18" subjects_at_risk="255"/>
                <counts group_id="E2" events="40" subjects_affected="32" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="255"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="255"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="255"/>
                <counts group_id="E2" events="19" subjects_affected="14" subjects_at_risk="266"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT02256436
org study id: 3475-045
secondary id: 2014-002009-40
secondary id: 152903
secondary id: MK-3475-045
nct id: NCT02256436
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Participants with metastatic or locally advanced/unresectable urothelial cancer that has
      recurred or progressed following platinum-based chemotherapy will be randomly assigned to
      receive Investigator's choice of paclitaxel, docetaxel, or vinflunine (Control), or
      pembrolizumab. The primary study hypotheses are that pembrolizumab will prolong Overall
      Survival (OS) and Progression-free Survival (PFS) compared to paclitaxel, docetaxel, or
      vinflunine.
For the purposes of this study, participants with a programmed cell death-ligand 1 (PD-L1)
      combined positive score (CPS) ≥10% were considered to have a strongly PD-L1 positive tumor
      status and participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor
      status.

      Effective with Amendment 15, eligible participants who are allocated to the Control arm
      (Investigator's Choice) and experience disease progression will be provided with the
      opportunity to switch over to receive pembrolizumab 200 mg one time every three weeks (Q3W)
      for up to two years of treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016.
measure: Overall Survival (OS) - All Participants
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016.
measure: PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.
measure: OS - Participants With PD-L1 Positive Tumors
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.
measure: PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.
measure: OS - Participants With Strongly PD-L1 Positive Tumors
time frame: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
description: OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.
measure: Number of Participants Who Experienced an Adverse Event (AE)
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was reported for each arm.
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm.
measure: Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: ORR Per RECIST 1.1 - All Participants
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.
measure: PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: PFS Per mRECIST - Participants With PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: PFS Per mRECIST - All Participants
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in all randomized participants up through the final analysis database cut-off date of 26-Oct-2017.
measure: ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: ORR Per mRECIST - Participants With PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017.
measure: ORR Per mRECIST - All Participants
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017.
measure: Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on BICR and was analyzed using the Kaplan-Meier method.
measure: DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on BICR and was analyzed using the Kaplan-Meier method.
measure: DOR Per RECIST 1.1 - All Participants
time frame: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
description: For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants based on BICR and was analyzed using the Kaplan-Meier method.
arm group label: Control
arm group type: Active Comparator
description: Participants receive paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experience disease progression may be able to switch over to receive pembrolizumab 200 mg Q3W for up to 35 treatment administrations (up to approximately 2 years).
arm group label: Pembrolizumab
arm group type: Experimental
description: Participants receive pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to approximately 1 additional year).
intervention type: Biological
intervention name: pembrolizumab
description: IV infusion
arm group label: Pembrolizumab
other name: MK-3475
other name: KEYTRUDA®
intervention type: Drug
intervention name: paclitaxel
description: IV infusion
arm group label: Control
intervention type: Drug
intervention name: vinflunine
description: IV infusion
arm group label: Control
intervention type: Drug
intervention name: docetaxel
description: IV infusion
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Australia
country: Austria
country: Belgium
country: Canada
country: Chile
country: Denmark
country: France
country: Germany
country: Hungary
country: Ireland
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: New Zealand
country: Norway
country: Peru
country: Poland
country: Portugal
country: Puerto Rico
country: Romania
country: Singapore
country: Spain
country: Sweden
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical trials Information
responsible party type: Sponsor
mesh term: Paclitaxel
mesh term: Docetaxel
mesh term: Pembrolizumab
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 