<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/NCT02212730</url>
  </required_header>
  <id_info>
    <org_study_id>3475-031</org_study_id>
    <secondary_id>2014-002526-12</secondary_id>
    <secondary_id>MK-3475-031</secondary_id>
    <secondary_id>KEYNOTE-031</secondary_id>
    <nct_id>NCT02212730</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)</brief_title>
  <official_title>A Clinical Trial to Evaluate the Effect of Neoadjuvant MK-3475 (Pembrolizumab) Therapy on Intratumoral Immune Infiltrates in Renal Cell Cancer (RCC) Patients Undergoing Surgical Resection</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_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab&#xD;
      (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are&#xD;
      that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that&#xD;
      pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic&#xD;
      infiltration in at least 30% of participants with RCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated early due to low enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">December 3, 2014</start_date>
  <completion_date type="Actual">July 5, 2019</completion_date>
  <primary_completion_date type="Actual">July 5, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen</measure>
    <time_frame>Up to Week 16</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Discontinued Treatment Due to an Adverse Event</measure>
    <time_frame>Up to 56 weeks</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</measure>
    <time_frame>Baseline and Week 7</time_frame>
    <description>The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Renal Cell Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant Pembrolizumab + RCC Resection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RCC Resection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab Pre-Resection</intervention_name>
    <description>200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles</description>
    <arm_group_label>Neoadjuvant Pembrolizumab + RCC Resection</arm_group_label>
    <other_name>KEYTRUDA®</other_name>
    <other_name>MK-3475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical Resection</intervention_name>
    <description>Standard of care surgical resection of RCC tumor</description>
    <arm_group_label>Neoadjuvant Pembrolizumab + RCC Resection</arm_group_label>
    <arm_group_label>RCC Resection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab Post-Resection</intervention_name>
    <description>200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles</description>
    <arm_group_label>Neoadjuvant Pembrolizumab + RCC Resection</arm_group_label>
    <arm_group_label>RCC Resection</arm_group_label>
    <other_name>KEYTRUDA®</other_name>
    <other_name>MK-3475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (&gt;= T1b),&#xD;
             not previously treated, and be a candidate for operative tumor resection&#xD;
&#xD;
          -  Be willing and able to undergo pre-treatment baseline image-guided core biopsy of&#xD;
             their primary RCC&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Scale&#xD;
&#xD;
          -  Demonstrate adequate organ function&#xD;
&#xD;
          -  Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates&#xD;
             non-pregnant state, and agrees to use two acceptable methods of birth control&#xD;
             throughout the trial, until 120 days after the last dose of treatment&#xD;
&#xD;
          -  Male with female partner of childbearing potential agrees to use adequate method of&#xD;
             contraception throughout study, until 120 days after last dose of treatment or last&#xD;
             blood draw.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating in, or has participated in a study with an investigational&#xD;
             agent or device within 4 weeks prior to first dose of study therapy&#xD;
&#xD;
          -  Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any&#xD;
             other form of immunosuppressive therapy within 4 weeks prior to first dose of study&#xD;
             therapy&#xD;
&#xD;
          -  Has had prior chemotherapy, targeted small molecule, or radiation therapy for&#xD;
             treatment of RCC&#xD;
&#xD;
          -  Has a known additional (other than RCC) malignancy that is progressing or requires&#xD;
             active treatment&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis&#xD;
&#xD;
          -  Has an active, or documented history of autoimmune disease, with the exceptions of&#xD;
             vitiligo or resolved childhood asthma/atopy&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required treatment with steroids or&#xD;
             current pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systematic therapy&#xD;
&#xD;
          -  Is receiving anticoagulant therapy, with the exception of low dosage aspirin&#xD;
&#xD;
          -  Has severe cardiovascular disease or symptomatic ischemic heart disease&#xD;
&#xD;
          -  Has hepatic decompensation&#xD;
&#xD;
          -  Has uncontrolled thyroid dysfunction&#xD;
&#xD;
          -  Has uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders&#xD;
&#xD;
          -  Female is pregnant or breastfeeding&#xD;
&#xD;
          -  Is expecting to conceive children within the projected maximum duration of the trial,&#xD;
             extending through 120 days after the last dose of treatment or the last blood draw&#xD;
&#xD;
          -  Has received prior therapy with any antibody or drug (including ipilimumab)&#xD;
             specifically targeting T-cell co-stimulation or checkpoint pathway&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Has known active hepatitis B or C&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to screening&#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>Belgium</country>
    <country>Canada</country>
    <country>Singapore</country>
  </removed_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <results_first_submitted>June 22, 2020</results_first_submitted>
  <results_first_submitted_qc>June 22, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 16, 2020</results_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Renal Cell</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>September 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT02212730/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
          <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
        </group>
        <group group_id="P2">
          <title>RCC Resection</title>
          <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Neoadjuvant Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Underwent RCC</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Post-RCC Pembrolizumab</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Tumor not of the required cell histology</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression prior to RCC surgery</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
          <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
        </group>
        <group group_id="B2">
          <title>RCC Resection</title>
          <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="10"/>
          </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="66.5" spread="5.2"/>
                    <measurement group_id="B2" value="55.3" spread="9.1"/>
                    <measurement group_id="B3" value="62.0" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Up to Week 16</time_frame>
        <population>Per protocol, the analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.</description>
          <population>Per protocol, the analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Discontinued Treatment Due to an Adverse Event</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.</description>
        <time_frame>Up to 56 weeks</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of pembrolizumab. Participants in the RCC Resection arm only received pembrolizumab if they enrolled under protocol amendment 04. Counts were based on which course of pembrolizumab (neoadjuvant or post-resection) a participant was receiving at the time of discontinuation.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Treatment Due to an Adverse Event</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of pembrolizumab. Participants in the RCC Resection arm only received pembrolizumab if they enrolled under protocol amendment 04. Counts were based on which course of pembrolizumab (neoadjuvant or post-resection) a participant was receiving at the time of discontinuation.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>During neoadjuvant pembrolizumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>During post-RCC resection pembrolizumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration</title>
        <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration</title>
          <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
        <description>The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
          <description>The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
          <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
        <description>The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
          <description>The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.</description>
          <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab</title>
        <description>The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab</title>
          <description>The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.</description>
          <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
        <description>The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
          <description>The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
          <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
        <description>The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
          <group group_id="O2">
            <title>RCC Resection</title>
            <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab</title>
          <description>The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.</description>
          <population>The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration</title>
        <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration</title>
          <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration</title>
        <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
        <time_frame>Baseline and Week 7</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
            <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration</title>
          <description>The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 77 weeks</time_frame>
      <desc>Adverse events are reported only for participants who received treatment as described in each arm's description. Deaths are reported for all participants who enrolled, regardless of whether they received treatment.&#xD;
Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless it resulted in hospitalization or death.</desc>
      <group_list>
        <group group_id="E1">
          <title>Neoadjuvant Pembrolizumab + RCC Resection</title>
          <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04. Adverse events in this arm are only counted until 30 days after RCC resection for non-serious adverse events, 90 days for serious adverse events, or until a participant started the post-surgery course of pembrolizumab, whichever occurred first. Deaths are counted from the time of enrollment until a participant started the post-surgery course of pembrolizumab.</description>
        </group>
        <group group_id="E2">
          <title>Neoadjuvant Pembrolizumab+Resection+Post-Surgery Pembrolizumab</title>
          <description>Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04. Adverse events and deaths in this arm are only counted after a participant started the post-surgery course of pembrolizumab.</description>
        </group>
        <group group_id="E3">
          <title>SOC RCC Resection</title>
          <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04. Adverse events in this arm are only counted until 30 days after RCC resection for non-serious adverse events, 90 days for serious adverse events, or until a participant started the post-surgery course of pembrolizumab, whichever occurred first. Deaths are counted from the time of enrollment until a participant started the post-surgery course of pembrolizumab.</description>
        </group>
        <group group_id="E4">
          <title>RCC Resection + Post-Resection Pembrolizumab</title>
          <description>Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04. Adverse events and deaths in this arm are only counted after a participant started the post-surgery course of pembrolizumab.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 22.0</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="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders</sub_title>
                <description>Due to the small sample size for this study, we are not disclosing the specific Adverse Event term for this Adverse Event due to patient confidentiality concerns.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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 Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02212730
org study id: 3475-031
secondary id: 2014-002526-12
secondary id: MK-3475-031
secondary id: KEYNOTE-031
nct id: NCT02212730
lead sponsor: 
has dmc: No
is fda regulated device: No
This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab
      (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are
      that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that
      pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic
      infiltration in at least 30% of participants with RCC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
time frame: Up to Week 16
description: An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
measure: Number of Participants Who Discontinued Treatment Due to an Adverse Event
time frame: Up to 56 weeks
description: An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
time frame: Baseline and Week 7
description: The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
time frame: Baseline and Week 7
description: The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
time frame: Baseline and Week 7
description: The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.
measure: Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
time frame: Baseline and Week 7
description: The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
measure: Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
time frame: Baseline and Week 7
description: The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
measure: Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
time frame: Baseline and Week 7
description: The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
measure: Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
time frame: Baseline and Week 7
description: The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
measure: Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
time frame: Baseline and Week 7
description: The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
arm group label: Neoadjuvant Pembrolizumab + RCC Resection
arm group type: Experimental
description: Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.
arm group label: RCC Resection
arm group type: Experimental
description: Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.
intervention type: Drug
intervention name: Pembrolizumab Pre-Resection
description: 200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
arm group label: Neoadjuvant Pembrolizumab + RCC Resection
other name: KEYTRUDA®
other name: MK-3475
intervention type: Procedure
intervention name: Surgical Resection
description: Standard of care surgical resection of RCC tumor
arm group label: Neoadjuvant Pembrolizumab + RCC Resection
arm group label: RCC Resection
intervention type: Drug
intervention name: Pembrolizumab Post-Resection
description: 200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
arm group label: Neoadjuvant Pembrolizumab + RCC Resection
arm group label: RCC Resection
other name: KEYTRUDA®
other name: MK-3475
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: Belgium
country: Canada
country: Singapore
responsible party type: Sponsor
mesh term: Carcinoma, Renal Cell
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: 