<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/NCT02255097</url>
  </required_header>
  <id_info>
    <org_study_id>3475-055</org_study_id>
    <secondary_id>2014-002447-18</secondary_id>
    <nct_id>NCT02255097</nct_id>
  </id_info>
  <brief_title>Study of MK-3475 (Pembrolizumab) in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma After Treatment With Platinum-based and Cetuximab Therapy (MK-3475-055/KEYNOTE-055)</brief_title>
  <official_title>A Phase II Clinical Trial of Single Agent Pembrolizumab (MK-3475) in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Who Have Failed Platinum and Cetuximab</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>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study of single-agent pembrolizumab (MK-3475) in participants with recurrent and/or&#xD;
      metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on&#xD;
      platinum-based and cetuximab therapy. The primary study hypothesis is that pembrolizumab will&#xD;
      provide a clinically meaningful objective response rate (ORR).&#xD;
&#xD;
      With protocol amendment 05 (02-Jan-2018), once study participants have achieved the study&#xD;
      objective or the study has ended, participants will be discontinued from this study and&#xD;
      enrolled in an extension study to continue protocol-defined assessments and treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2014</start_date>
  <completion_date type="Actual">June 18, 2021</completion_date>
  <primary_completion_date type="Actual">April 22, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Experiencing an Adverse Event (AE)</measure>
    <time_frame>Up to 27 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Discontinuing Study Drug Due to an AE</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a positive PD-L1 expression status were evaluated for PFS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in All Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a positive PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</measure>
    <time_frame>Up to 76.9 months</time_frame>
    <description>Participants with a strong PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">172</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically- or cytologically-confirmed recurrent or metastatic HNSCC of the oral&#xD;
             cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local&#xD;
             therapies&#xD;
&#xD;
          -  Tumor progression or recurrence within 6 months of the last dose of any number of&#xD;
             platinum-based and cetuximab therapy lines in the adjuvant, primary, recurrent, or&#xD;
             metastatic setting; must be resistant (not responding) to both platinum and cetuximab&#xD;
&#xD;
          -  Available tissue for biomarker analysis&#xD;
&#xD;
          -  Measurable disease based on RECIST 1.1 as determined by central review&#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 have a negative urine or serum&#xD;
             pregnancy test and must be willing to use 2 adequate methods of contraception starting&#xD;
             with the screening visit through 120 days after the last dose of pembrolizumab&#xD;
&#xD;
          -  Male participants with a female partner(s) of childbearing potential must be willing&#xD;
             to use 2 adequate methods of contraception from screening through 120 days after the&#xD;
             last dose of pembrolizumab&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Disease that is suitable for local therapy administered with curative intent&#xD;
&#xD;
          -  Currently receiving treatment in a study of an investigational agent or using an&#xD;
             investigational device &lt;= 4 weeks prior to the first dose of trial medication&#xD;
&#xD;
          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form&#xD;
             of immunosuppressive therapy within 7 days prior to the first dose of trial medication&#xD;
&#xD;
          -  Not recovered from AEs due to a previously administered therapy&#xD;
&#xD;
          -  Known additional malignancy that is progressing or requires active treatment excluding&#xD;
             basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has&#xD;
             undergone potentially curative therapy or in situ cancer&#xD;
&#xD;
          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in past 2 years&#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 medication&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Hepatitis B or C&#xD;
&#xD;
          -  Received 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>Denmark</country>
    <country>Norway</country>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trials Information</description>
  </link>
  <results_reference>
    <citation>Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Shu X, Cheng JD, Haddad R. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol. 2017 May 10;35(14):1542-1549. doi: 10.1200/JCO.2016.70.1524. Epub 2017 Mar 22.</citation>
    <PMID>28328302</PMID>
  </results_reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <results_first_submitted>April 20, 2017</results_first_submitted>
  <results_first_submitted_qc>June 7, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 6, 2017</results_first_posted>
  <last_update_submitted>June 23, 2022</last_update_submitted>
  <last_update_submitted_qc>June 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Programmed Cell Death-1 (PD1, PD-1)</keyword>
  <keyword>Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT02255097/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. Per protocol, response or progression during the second course of pembrolizumab was not counted towards efficacy outcome measures and adverse events during the second course of pembrolizumab were not counted towards safety outcome measures.</recruitment_details>
      <pre_assignment_details>Final analyses for all primary outcome measures were done at the protocol-specified primary outcome measure met date. The analyses for all secondary outcome measures and the collection of adverse events were updated at the end of study date.&#xD;
One participant allocated to receive pembrolizumab did not receive treatment. This participant was not eligible for safety or efficacy analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="172"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="171"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Second Course of Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="172"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="151"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participation in Study Discontinued by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Allocated but not treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline population included all participants allocated to receive ≥1 dose of pembrolizumab.</population>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="172"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.1" spread="9.9"/>
                  </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="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="138"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="153"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="153"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status</title>
          <description>Participants were assessed for their PD-L1 tumor expression status by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a tumor proportion score (TPS) were classified as follows: ≥50% = PD-L1 strongly positive; 1-49% = PD-L1 weakly positive; and &lt;1% = PD-L1 negative.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>≥50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥1 - &lt;50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&lt;1%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
        <description>ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 36 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
          <description>ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment</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="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.4" lower_limit="11.2" upper_limit="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>null hypothesis (H0): p ≤ 0.05 versus alternate hypothesis (H1): p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 36 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</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="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.3" lower_limit="15.0" upper_limit="42.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Experiencing an Adverse Event (AE)</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
        <time_frame>Up to 27 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing an Adverse Event (AE)</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
          <population>All participants who received at least one dose of study treatment</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="166"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Discontinuing Study Drug Due to an AE</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
        <time_frame>Up to 24 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Discontinuing Study Drug Due to an AE</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.</description>
          <population>All participants who received at least one dose of study treatment</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥1%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥1%</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="121"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" lower_limit="11.8" upper_limit="26.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors</title>
        <description>Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a HPV-positive tumor</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors</title>
          <description>Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment with a HPV-positive tumor</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="71"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.1" lower_limit="7.0" upper_limit="24.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0027</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
        <description>ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
          <description>ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment</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="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.4" lower_limit="11.2" upper_limit="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥1%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥1%</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="121"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" lower_limit="11.8" upper_limit="26.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to &lt;10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</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="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.3" lower_limit="15.0" upper_limit="42.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distribution</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>exact binomial distribution</method>
            <method_desc>H0: p ≤ 0.05 versus H1: p &gt; 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
        <description>DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a best overall response as confirmed complete response or partial response</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
          <description>DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
          <population>All participants who received at least one dose of study treatment with a best overall response as confirmed complete response or partial response</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="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" lower_limit="2.8" upper_limit="NA">NA=Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a combined positive score ≥1% and a best overall response as confirmed complete response or partial response</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
          <population>All participants who received at least one dose of study treatment with a combined positive score ≥1% and a best overall response as confirmed complete response or partial response</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" lower_limit="2.8" upper_limit="NA">NA=Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50% and a best overall response as confirmed complete response or partial response</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50% and a best overall response as confirmed complete response or partial response</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.8" lower_limit="4.2" upper_limit="NA">NA = Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
        <description>PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants</title>
          <description>PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment</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="171"/>
              </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="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a positive PD-L1 expression status were evaluated for PFS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a combined positive score ≥1%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a positive PD-L1 expression status were evaluated for PFS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment with a combined positive score ≥1%</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="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="2.0" upper_limit="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of &gt;5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</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="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="1.8" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in All Participants</title>
        <description>OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All 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 by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in All Participants</title>
          <description>OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment</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="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" lower_limit="6.6" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a positive PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a combined positive score ≥1%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a positive PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment with a combined positive score ≥1%</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="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" lower_limit="6.2" upper_limit="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
        <description>Participants with a strong PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
        <time_frame>Up to 76.9 months</time_frame>
        <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants</title>
          <description>Participants with a strong PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.</description>
          <population>All participants who received at least one dose of study treatment with a tumor proportion score ≥50%</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="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" lower_limit="4.0" upper_limit="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First Course: Up to 76.9 months Second Course: Up to 53.3 months First and second course dosing occurred concurrently</time_frame>
      <desc>All-cause mortality (ACM)=all allocated participants; AEs=all participants who received ≥1 dose of study treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded. Per protocol, collection of AEs and ACM were planned for both first and second courses.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment.</description>
        </group>
        <group group_id="E2">
          <title>Pembrolizumab Second Course</title>
          <description>Participants who met the criteria for re-treatment received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 1 year of treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</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="153" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="87" subjects_at_risk="171"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </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="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Salivary duct inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Swelling face</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Empyema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Endocarditis bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="15" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia escherichia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia staphylococcal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pseudomonas infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Staphylococcal sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tracheitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastrointestinal stoma complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Radiation oesophagitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tracheal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Traumatic fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Clostridium test positive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cachexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Type 1 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Appendix cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Infected neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Keratoacanthoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Amyotrophic lateral sclerosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cranial nerve paralysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Increased upper airway secretion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Laryngeal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Stridor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.0</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="158" subjects_at_risk="171"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </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="35" subjects_affected="32" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="34" subjects_affected="32" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="46" subjects_affected="42" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="38" subjects_affected="24" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="23" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lip dry</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="37" subjects_affected="34" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="71" subjects_affected="67" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="12" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Stoma site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="33" subjects_affected="33" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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="36" subjects_affected="30" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="20" subjects_affected="16" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="14" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="14" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="41" subjects_affected="29" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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="33" subjects_affected="27" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="21" subjects_affected="18" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="18" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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="39" subjects_affected="38" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="26" subjects_affected="23" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Psoriasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="20" subjects_affected="17" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="17" subjects_affected="11" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="17" subjects_affected="16" subjects_at_risk="171"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="171"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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/NCT02255097
org study id: 3475-055
secondary id: 2014-002447-18
nct id: NCT02255097
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a study of single-agent pembrolizumab (MK-3475) in participants with recurrent and/or
      metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on
      platinum-based and cetuximab therapy. The primary study hypothesis is that pembrolizumab will
      provide a clinically meaningful objective response rate (ORR).

      With protocol amendment 05 (02-Jan-2018), once study participants have achieved the study
      objective or the study has ended, participants will be discontinued from this study and
      enrolled in an extension study to continue protocol-defined assessments and treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
time frame: Up to 36 months
description: ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 36 months
description: Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
measure: Number of Participants Experiencing an Adverse Event (AE)
time frame: Up to 27 months
description: An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
measure: Number of Participants Discontinuing Study Drug Due to an AE
time frame: Up to 24 months
description: An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors
time frame: Up to 76.9 months
description: Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
measure: Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
time frame: Up to 76.9 months
description: ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
measure: Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
measure: Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
measure: Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
time frame: Up to 76.9 months
description: DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
measure: Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
measure: Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
measure: Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
time frame: Up to 76.9 months
description: PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
measure: Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a positive PD-L1 expression status were evaluated for PFS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
measure: Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
measure: Overall Survival (OS) in All Participants
time frame: Up to 76.9 months
description: OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
measure: Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a positive PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
measure: Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
time frame: Up to 76.9 months
description: Participants with a strong PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
arm group label: Pembrolizumab
arm group type: Experimental
description: Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
intervention type: Biological
intervention name: pembrolizumab
arm group label: Pembrolizumab
other name: MK-3475
other name: KEYTRUDA®
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: Denmark
country: Norway
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trials Information
citation: Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Shu X, Cheng JD, Haddad R. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol. 2017 May 10;35(14):1542-1549. doi: 10.1200/JCO.2016.70.1524. Epub 2017 Mar 22.
PMID: 28328302
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Pembrolizumab
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 