<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/NCT02252042</url>
  </required_header>
  <id_info>
    <org_study_id>3475-040</org_study_id>
    <secondary_id>MK-3475-040</secondary_id>
    <secondary_id>2014-001749-26</secondary_id>
    <nct_id>NCT02252042</nct_id>
  </id_info>
  <brief_title>Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)</brief_title>
  <official_title>A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck 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>
      This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment&#xD;
      (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and&#xD;
      neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either&#xD;
      pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is&#xD;
      that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 17, 2014</start_date>
  <completion_date type="Actual">August 15, 2022</completion_date>
  <primary_completion_date type="Actual">May 15, 2017</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>Initial Overall Survival (OS) for All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Updated Final OS for All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Per RECIST 1.1 in All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) Per RECIST 1.1 in All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP) Per RECIST 1.1 in All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per Modified RECIST in All Participants</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 2 years</time_frame>
    <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants</measure>
    <time_frame>Up to approximately 33 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 33 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants</measure>
    <time_frame>Up to approximately 30 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS</measure>
    <time_frame>Up to approximately 30 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">495</enrollment>
  <condition>Head and Neck Squamous Cell Cancer</condition>
  <arm_group>
    <arm_group_label>Pembroliziumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. 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 for up to approximately 1 additional year at the investigator's discretion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200 mg intravenous (IV) on Day 1 of each 3-week cycle.</description>
    <arm_group_label>Pembroliziumab</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle</description>
    <arm_group_label>Standard Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>75 mg/m^2 IV on Day 1 of each 3- week cycle</description>
    <arm_group_label>Standard Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
    <arm_group_label>Standard Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has histologically- or cytologically-confirmed recurrent disease not amenable to&#xD;
             curative treatment with local or systemic therapy, or metastatic (disseminated) head&#xD;
             and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and&#xD;
             larynx that is considered incurable by local therapies&#xD;
&#xD;
          -  Failure of prior platinum therapy&#xD;
&#xD;
          -  Radiographically-measurable disease based on RECIST 1.1&#xD;
&#xD;
          -  Tumor tissue available for PD-L1 biomarker analysis&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Female participants of childbearing potential must be willing to use 2 methods of&#xD;
             birth control or abstain from heterosexual activity for the course of the study&#xD;
             through 120 days after last dose of pembrolizumab or through 120-180 days after the&#xD;
             last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of&#xD;
             care&#xD;
&#xD;
          -  Male participants must agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 120 days after last dose of pembrolizumab or&#xD;
             through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab,&#xD;
             acccording to local standard of care&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Disease 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 randomization&#xD;
&#xD;
          -  Previously treated with 3 or more systemic regimens given for recurrent and/or&#xD;
             metastatic disease&#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 therapy&#xD;
&#xD;
          -  Not recovered from adverse events due to therapy more than 4 weeks earlier&#xD;
&#xD;
          -  Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day&#xD;
             1, or not recovered from adverse events due to agents administered more than 4 weeks&#xD;
             earlier&#xD;
&#xD;
          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2&#xD;
             weeks prior to study Day 1&#xD;
&#xD;
          -  Diagnosed and/or treated additional malignancy within 5 years of randomization, with&#xD;
             the exception of curatively-treated basal cell or squamous cell carcinoma of the skin,&#xD;
             and/or curatively-resected in situ cervical and/or breast cancers&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic therapy in the past 2 years with&#xD;
             modifying agents, corticosteroids, or immunosuppressive agents&#xD;
&#xD;
          -  Active central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Active, non-infectious pneumonitis&#xD;
&#xD;
          -  Active infection requiring systemic therapy&#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 trial therapy according to local standard of care&#xD;
&#xD;
          -  Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously&#xD;
             participated in a Merck pembrolizumab (MK-3475) trial&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Hepatitis B or C&#xD;
&#xD;
          -  Live vaccine within 30 days of planned start of study therapy&#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>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Lithuania</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Puerto Rico</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://www.merckclinicaltrials.com/</url>
    <description>Merck Clinical Trials Information</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>May 4, 2018</results_first_submitted>
  <results_first_submitted_qc>August 10, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 13, 2018</results_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Squamous cell carcinoma</keyword>
  <keyword>Head and neck carcinoma</keyword>
  <keyword>Programmed Cell Death-1 (PD1, PD-1),</keyword>
  <keyword>Programmed Death-Ligand 1 (PDL1, PD-L1)</keyword>
  <keyword>Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Cetuximab</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 3, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT02252042/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>495 participants were randomized 1:1 to receive either pembrolizumab or standard treatment. Per protocol, response/progression or adverse events (AEs) that occurred during the second course of pembrolizumab were not counted towards efficacy outcome measures or safety outcome measures, respectively.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
        </group>
        <group group_id="P2">
          <title>Standard Treatment</title>
          <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="247"/>
                <participants group_id="P2" count="248"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received First Course of Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="246">1 participant was randomized but did not receive study treatment.</participants>
                <participants group_id="P2" count="234">14 participants were randomized but did not receive study treatment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Second Course of Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <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="247"/>
                <participants group_id="P2" count="248"/>
              </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="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="209"/>
                <participants group_id="P2" count="217"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Transferred to Extension Study</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did Not Continue on Extension Study</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
        </group>
        <group group_id="B2">
          <title>Standard Treatment</title>
          <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</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="247"/>
            <count group_id="B2" value="248"/>
            <count group_id="B3" value="495"/>
          </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="60.3" spread="9.8"/>
                    <measurement group_id="B2" value="60.2" spread="8.6"/>
                    <measurement group_id="B3" value="60.2" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="207"/>
                    <measurement group_id="B2" value="205"/>
                    <measurement group_id="B3" value="412"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="182"/>
                    <measurement group_id="B2" value="195"/>
                    <measurement group_id="B3" value="377"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>The race of participants is presented.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="206"/>
                    <measurement group_id="B2" value="207"/>
                    <measurement group_id="B3" value="413"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS)</title>
          <description>Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a TPS ≥50% were classified as PD-L1 strongly positive and participants with a TPS &lt;50% were classified as not strongly positive.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>TPS = 0%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="103"/>
                    <measurement group_id="B2" value="93"/>
                    <measurement group_id="B3" value="196"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1% ≤ TPS &lt;50%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="87"/>
                    <measurement group_id="B3" value="166"/>
                  </measurement_list>
                </category>
                <category>
                  <title>TPS ≥ 50%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="129"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)</title>
          <description>Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory &amp; able to carry out work of a light or sedentary nature; Grade 2: Ambulatory &amp; capable of all selfcare but unable to carry out any work activities, up &amp; about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>EGOG PS=0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="139"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG PS=1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="176"/>
                    <measurement group_id="B2" value="179"/>
                    <measurement group_id="B3" value="355"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG PS=2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Human Papillomavirus (HPV) Tumor Status</title>
          <description>Participants were assessed for the presence or absence of HPV in their tumors.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Positive HPV Status</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="118"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Negative HPV Status</title>
                  <measurement_list>
                    <measurement group_id="B1" value="186"/>
                    <measurement group_id="B2" value="191"/>
                    <measurement group_id="B3" value="377"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>PD-L1 Combined Positive Score (CPS) Status</title>
          <description>Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a CPS ≥1 were classified as PD-L1 positive and participants with a CPS &lt;1 were classified as PD-L1 negative.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>PD-L1 CPS &lt;1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PD-L1 CPS ≥1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="196"/>
                    <measurement group_id="B2" value="191"/>
                    <measurement group_id="B3" value="387"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Initial Overall Survival (OS) for All Participants</title>
        <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Initial Overall Survival (OS) for All Participants</title>
          <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.4" lower_limit="6.5" upper_limit="9.4"/>
                    <measurement group_id="O2" value="7.1" lower_limit="5.9" upper_limit="8.1"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03160</p_value>
            <method>Log Rank</method>
            <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>0.67</ci_lower_limit>
            <ci_upper_limit>1.01</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Updated Final OS for All Participants</title>
        <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Updated Final OS for All Participants</title>
          <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.4" lower_limit="6.4" upper_limit="9.4"/>
                    <measurement group_id="O2" value="6.9" lower_limit="5.9" upper_limit="8.0"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.01605</p_value>
            <p_value_desc>Nominal p-value</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.80</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.65</ci_lower_limit>
            <ci_upper_limit>0.98</ci_upper_limit>
            <estimate_desc>Nominal HR. Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)</title>
        <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)</title>
          <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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="196"/>
                <count group_id="O2" value="191"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" lower_limit="6.9" upper_limit="11.4"/>
                    <measurement group_id="O2" value="7.1" lower_limit="5.7" upper_limit="8.3"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.00493</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.58</ci_lower_limit>
            <ci_upper_limit>0.93</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="2.1" upper_limit="2.3"/>
                    <measurement group_id="O2" value="2.3" lower_limit="2.1" upper_limit="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.32504</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.79</ci_lower_limit>
            <ci_upper_limit>1.16</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
        <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
          <description>PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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="196"/>
                <count group_id="O2" value="191"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="2.1" upper_limit="3.0"/>
                    <measurement group_id="O2" value="2.3" lower_limit="2.1" upper_limit="3.0"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.07736</p_value>
            <method>Log Rank</method>
            <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>0.69</ci_lower_limit>
            <ci_upper_limit>1.06</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a single covariate</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Per RECIST 1.1 in All Participants</title>
        <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Per RECIST 1.1 in All Participants</title>
          <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.6" lower_limit="10.4" upper_limit="19.6"/>
                    <measurement group_id="O2" value="10.1" lower_limit="6.6" upper_limit="14.5"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0610</p_value>
            <method>Log Rank</method>
            <method_desc>H0: difference in %=0; H1: difference in %&gt;0</method_desc>
            <param_type>Difference in percentages</param_type>
            <param_value>4.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.2</ci_lower_limit>
            <ci_upper_limit>10.6</ci_upper_limit>
            <estimate_desc>Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
        <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
          <description>ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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="196"/>
                <count group_id="O2" value="191"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.3" lower_limit="12.3" upper_limit="23.4"/>
                    <measurement group_id="O2" value="9.9" lower_limit="6.1" upper_limit="15.1"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0171</p_value>
            <method>Log Rank</method>
            <method_desc>H0: difference in %=0; H1: difference in %&gt;0</method_desc>
            <param_type>Difference in percentages</param_type>
            <param_value>7.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>14.6</ci_upper_limit>
            <estimate_desc>Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) Per RECIST 1.1 in All Participants</title>
        <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) Per RECIST 1.1 in All Participants</title>
          <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.4" lower_limit="2.7" upper_limit="18.4"/>
                    <measurement group_id="O2" value="5.0" lower_limit="1.4" upper_limit="18.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
        <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
          <description>For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.4" lower_limit="2.7" upper_limit="18.4"/>
                    <measurement group_id="O2" value="9.6" lower_limit="1.4" upper_limit="18.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression (TTP) Per RECIST 1.1 in All Participants</title>
        <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression (TTP) Per RECIST 1.1 in All Participants</title>
          <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="2.1" upper_limit="3.3"/>
                    <measurement group_id="O2" value="2.2" lower_limit="2.1" upper_limit="3.4"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.14545</p_value>
            <p_value_desc>p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</p_value_desc>
            <method>Log Rank</method>
            <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>0.70</ci_lower_limit>
            <ci_upper_limit>1.12</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
        <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
          <description>TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="196"/>
                <count group_id="O2" value="191"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="2.1" upper_limit="3.5"/>
                    <measurement group_id="O2" value="2.3" lower_limit="2.1" upper_limit="3.4"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.05851</p_value>
            <p_value_desc>p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.81</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>1.06</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per Modified RECIST in All Participants</title>
        <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per Modified RECIST in All Participants</title>
          <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants. Participants are 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="247"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3.1" upper_limit="4.4"/>
                    <measurement group_id="O2" value="4.8" lower_limit="4.1" upper_limit="5.7"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.65759</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.04</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.86</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
        <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
        <time_frame>Up to approximately 2 years</time_frame>
        <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS</title>
          <description>PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (&gt;4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.</description>
          <population>The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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="196"/>
                <count group_id="O2" value="191"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" lower_limit="3.1" upper_limit="4.6"/>
                    <measurement group_id="O2" value="4.8" lower_limit="4.1" upper_limit="5.7"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.51982</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.01</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>1.26</ci_upper_limit>
            <estimate_desc>Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) &amp; PD-L1 status (Strongly Positive, Not Strongly Positive)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.</description>
        <time_frame>Up to approximately 33 months</time_frame>
        <population>The safety population consisted of all randomized participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.</description>
          <population>The safety population consisted of all randomized participants who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="246"/>
                <count group_id="O2" value="234"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="240"/>
                    <measurement group_id="O2" value="227"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.</description>
        <time_frame>Up to approximately 33 months</time_frame>
        <population>The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.</description>
          <population>The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="195"/>
                <count group_id="O2" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="193"/>
                    <measurement group_id="O2" value="178"/>
                  </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 in All Participants</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented.</description>
        <time_frame>Up to approximately 30 months</time_frame>
        <population>The safety population consisted of all randomized participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented.</description>
          <population>The safety population consisted of all randomized participants who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="246"/>
                <count group_id="O2" value="234"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="36"/>
                  </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 in Participants With PD-L1 ≥1% CPS</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.</description>
        <time_frame>Up to approximately 30 months</time_frame>
        <population>The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.</description>
          </group>
          <group group_id="O2">
            <title>Standard Treatment</title>
            <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.</description>
          <population>The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="195"/>
                <count group_id="O2" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to approximately 92 months</time_frame>
      <desc>All-Cause Mortality was reported for all randomized participants.&#xD;
Serious AEs and Other AEs were reported according to treatment course for all randomized participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms &quot;Neoplasm progression&quot;, &quot;Malignant neoplasm progression&quot; and &quot;Disease progression&quot; not related to study drug are excluded as AEs.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab First Course</title>
          <description>Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to approximately 24 months.</description>
        </group>
        <group group_id="E2">
          <title>Standard Treatment First Course</title>
          <description>Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.</description>
        </group>
        <group group_id="E3">
          <title>Pembrolizumab Second Course</title>
          <description>Eligible participants who stopped the initial course of pembrolizumab (200 mg IV Q3W for up to approximately 24 months) with SD or better but progressed after discontinuation initiated a second course of pembrolizumab at the investigator's discretion for up to approximately 1 additional year.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.0</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="228" subjects_at_risk="247"/>
                <counts group_id="E2" subjects_affected="243" subjects_at_risk="248"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="110" subjects_at_risk="246"/>
                <counts group_id="E2" subjects_affected="92" subjects_at_risk="234"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </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="5" subjects_affected="5" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Anaemia of malignant disease</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lymph node haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia of malignancy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Autoimmune colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Gastrointestinal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Incarcerated inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malignant dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oral discharge</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumoperitoneum</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="246"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Ill-defined disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Performance status decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cirrhosis alcoholic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Candida sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Colonic abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Disseminated tuberculosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Epiglottitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Infected fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Klebsiella infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oral bacterial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="22" subjects_at_risk="246"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stoma site infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Subcutaneous abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Alcohol poisoning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Post procedural fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Post procedural hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stoma site haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stoma site ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Tracheostomy malfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="4" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypophagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Kyphosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Soft tissue haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Astrocytoma, low grade</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Infected neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malignant melanoma in situ</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oropharyngeal neoplasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Paraneoplastic syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rectal cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="246"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Guillain-Barre syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vocal cord paresis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Asphyxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Eosinophilic pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Laryngeal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Laryngeal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oropharyngeal fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="246"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Respiratory disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Respiratory tract haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acute febrile neutrophilic dermatosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fungating wound</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stevens-Johnson syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Euthanasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Angiodysplasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="246"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Jugular vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 25.0</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="215" subjects_at_risk="246"/>
                <counts group_id="E2" subjects_affected="211" subjects_at_risk="234"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </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="77" subjects_affected="61" subjects_at_risk="246"/>
                <counts group_id="E2" events="72" subjects_affected="53" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="45" subjects_affected="41" subjects_at_risk="246"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="246"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="49" subjects_affected="43" subjects_at_risk="246"/>
                <counts group_id="E2" events="43" subjects_affected="37" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="57" subjects_affected="37" subjects_at_risk="246"/>
                <counts group_id="E2" events="51" subjects_affected="42" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="246"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="22" subjects_affected="21" subjects_at_risk="246"/>
                <counts group_id="E2" events="16" subjects_affected="15" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="45" subjects_affected="36" subjects_at_risk="246"/>
                <counts group_id="E2" events="52" subjects_affected="44" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="246"/>
                <counts group_id="E2" events="34" subjects_affected="26" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="28" subjects_affected="24" subjects_at_risk="246"/>
                <counts group_id="E2" events="34" subjects_affected="23" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="50" subjects_affected="40" subjects_at_risk="246"/>
                <counts group_id="E2" events="54" subjects_affected="42" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="53" subjects_affected="49" subjects_at_risk="246"/>
                <counts group_id="E2" events="81" subjects_affected="63" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="21" subjects_affected="17" subjects_at_risk="246"/>
                <counts group_id="E2" events="51" subjects_affected="36" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="38" subjects_affected="24" subjects_at_risk="246"/>
                <counts group_id="E2" events="36" subjects_affected="25" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="246"/>
                <counts group_id="E2" events="18" subjects_affected="13" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="16" subjects_affected="13" subjects_at_risk="246"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="29" subjects_affected="24" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="246"/>
                <counts group_id="E2" events="19" subjects_affected="13" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="24" subjects_affected="21" subjects_at_risk="246"/>
                <counts group_id="E2" events="25" subjects_affected="25" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="37" subjects_affected="31" subjects_at_risk="246"/>
                <counts group_id="E2" events="50" subjects_affected="45" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="246"/>
                <counts group_id="E2" events="14" subjects_affected="13" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="27" subjects_affected="23" subjects_at_risk="246"/>
                <counts group_id="E2" events="21" subjects_affected="19" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="246"/>
                <counts group_id="E2" events="25" subjects_affected="20" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="246"/>
                <counts group_id="E2" events="17" subjects_affected="16" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="15" subjects_at_risk="246"/>
                <counts group_id="E2" events="14" subjects_affected="12" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="24" subjects_affected="23" subjects_at_risk="246"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="24" subjects_affected="23" subjects_at_risk="246"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="246"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="246"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="25" subjects_affected="21" subjects_at_risk="246"/>
                <counts group_id="E2" events="25" subjects_affected="23" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="246"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="246"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="49" subjects_affected="43" subjects_at_risk="246"/>
                <counts group_id="E2" events="40" subjects_affected="37" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="33" subjects_affected="31" subjects_at_risk="246"/>
                <counts group_id="E2" events="31" subjects_affected="26" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="246"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="16" subjects_affected="15" subjects_at_risk="246"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="1" subjects_affected="1" subjects_at_risk="246"/>
                <counts group_id="E2" events="27" subjects_affected="27" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="246"/>
                <counts group_id="E2" events="28" subjects_affected="18" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="246"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="24" subjects_affected="19" subjects_at_risk="246"/>
                <counts group_id="E2" events="40" subjects_affected="17" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="33" subjects_affected="26" subjects_at_risk="246"/>
                <counts group_id="E2" events="92" subjects_affected="41" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="246"/>
                <counts group_id="E2" events="16" subjects_affected="12" subjects_at_risk="234"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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. Sponsor review can be expedited to meet publication timelines.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</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/NCT02252042
org study id: 3475-040
secondary id: MK-3475-040
secondary id: 2014-001749-26
nct id: NCT02252042
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment
      (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and
      neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either
      pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is
      that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard
      treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Initial Overall Survival (OS) for All Participants
time frame: Up to approximately 2 years
description: OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
measure: Updated Final OS for All Participants
time frame: Up to approximately 2 years
description: OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
time frame: Up to approximately 2 years
description: OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
time frame: Up to approximately 2 years
description: PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 2 years
description: PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
time frame: Up to approximately 2 years
description: ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 2 years
description: ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: Duration of Response (DOR) Per RECIST 1.1 in All Participants
time frame: Up to approximately 2 years
description: For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 2 years
description: For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: Time to Progression (TTP) Per RECIST 1.1 in All Participants
time frame: Up to approximately 2 years
description: TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 2 years
description: TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: PFS Per Modified RECIST in All Participants
time frame: Up to approximately 2 years
description: PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 2 years
description: PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
measure: Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
time frame: Up to approximately 33 months
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
measure: Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 33 months
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.
measure: Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
time frame: Up to approximately 30 months
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented.
measure: Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
time frame: Up to approximately 30 months
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.
arm group label: Pembroliziumab
arm group type: Experimental
description: Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. 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 for up to approximately 1 additional year at the investigator's discretion.
arm group label: Standard Treatment
arm group type: Active Comparator
description: Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
intervention type: Biological
intervention name: Pembrolizumab
description: 200 mg intravenous (IV) on Day 1 of each 3-week cycle.
arm group label: Pembroliziumab
other name: MK-3475
other name: KEYTRUDA®
intervention type: Drug
intervention name: Methotrexate
description: 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle
arm group label: Standard Treatment
intervention type: Drug
intervention name: Docetaxel
description: 75 mg/m^2 IV on Day 1 of each 3- week cycle
arm group label: Standard Treatment
intervention type: Biological
intervention name: Cetuximab
description: 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
arm group label: Standard Treatment
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: Belgium
country: Canada
country: France
country: Germany
country: Hungary
country: Ireland
country: Italy
country: Korea, Republic of
country: Lithuania
country: Mexico
country: Netherlands
country: Poland
country: Portugal
country: Puerto Rico
country: Russian Federation
country: Spain
country: Sweden
country: Switzerland
country: United Kingdom
country: United States
url: https://www.merckclinicaltrials.com/
description: Merck Clinical Trials Information
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Neoplasms, Squamous Cell
mesh term: Carcinoma, Squamous Cell
mesh term: Docetaxel
mesh term: Pembrolizumab
mesh term: Methotrexate
mesh term: Cetuximab
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: 