<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/NCT03029780</url>
  </required_header>
  <id_info>
    <org_study_id>CA209-800</org_study_id>
    <nct_id>NCT03029780</nct_id>
  </id_info>
  <brief_title>An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma</brief_title>
  <acronym>CheckMate 800</acronym>
  <official_title>Phase II, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bristol-Myers Squibb</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>
      The purpose of this study is to evaluate safety and efficacy of different administration&#xD;
      regimens of nivolumab plus ipilimumab in subjects with renal cell carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Actual">June 15, 2021</completion_date>
  <primary_completion_date type="Actual">November 27, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period</measure>
    <time_frame>From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)</time_frame>
    <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period</measure>
    <time_frame>From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)</time_frame>
    <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Participants With Drug Related Grade 3-5 Adverse Events</measure>
    <time_frame>From first dose to 30 days after last dose of study therapy (up to approximately 48 months)</time_frame>
    <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Participants With All Causality Grade 3-5 Adverse Events</measure>
    <time_frame>From first dose to 30 days after last dose of study therapy (up to approximately 48 months)</time_frame>
    <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)</time_frame>
    <description>The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)</time_frame>
    <description>The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab</measure>
    <time_frame>pre-dose on day 1 of cycle 2 and 4</time_frame>
    <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab</measure>
    <time_frame>EOI on day 1 of cycle 1, 2, and 4</time_frame>
    <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Co-Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab and Ipilimumab Co-Administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequential Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab and Ipilimumab Sequential Administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Opdivo</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Co-Administration</arm_group_label>
    <arm_group_label>Sequential Administration</arm_group_label>
    <other_name>Nivolumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Yervoy</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Co-Administration</arm_group_label>
    <arm_group_label>Sequential Administration</arm_group_label>
    <other_name>Ipilimumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please&#xD;
        visit www.BMSStudyConnect.com&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Advanced Renal Cell Carcinoma&#xD;
&#xD;
          -  Must have full activity or, if limited, must be able to walk and carry out light&#xD;
             activities such as light house work or office work&#xD;
&#xD;
          -  Must have at least 1 lesion with measurable disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with active central nervous system metastases&#xD;
&#xD;
          -  Subjects who received prior therapy with checkpoint inhibitor&#xD;
&#xD;
          -  Subjects with active, known or suspected autoimmune disease&#xD;
&#xD;
        Other protocol defined inclusion/exclusion criteria could apply&#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>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Specialists of North FL</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Iowa Hospitals And Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212-0000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Waratah</city>
        <state>New South Wales</state>
        <zip>2298</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Elizabeth Vale</city>
        <state>South Australia</state>
        <zip>5112</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Malvern</city>
        <state>Victoria</state>
        <zip>3144</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Arturo Lopez Perez</name>
      <address>
        <city>Santiago</city>
        <state>Metropolitana</state>
        <zip>7500921</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Internacional de Estudios Clinicos</name>
      <address>
        <city>Recoleta</city>
        <state>Santiago De Chile</state>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Chile</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <link>
    <url>https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm</url>
    <description>FDA Safety Alerts and Recalls</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>November 27, 2018</results_first_submitted>
  <results_first_submitted_qc>November 27, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 19, 2018</results_first_posted>
  <last_update_submitted>June 1, 2022</last_update_submitted>
  <last_update_submitted_qc>June 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2022</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</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03029780/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03029780/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>104 participants were randomized and treated</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm A: Fixed Ratio Combination</title>
          <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
        </group>
        <group group_id="P2">
          <title>Arm B: Sequential Combination</title>
          <description>Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="51"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Drug Toxicity</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event Unrelated to Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant request to discontinue study treatment</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Maximum clinical benefit</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant no longer meets study criteria</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reasons</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not reported</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All treated participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Arm A: Fixed Ratio Combination</title>
          <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
        </group>
        <group group_id="B2">
          <title>Arm B: Sequential Combination</title>
          <description>Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</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="52"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="104"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>All treated participants</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.2" spread="10.9"/>
                    <measurement group_id="B2" value="62.6" spread="9.9"/>
                    <measurement group_id="B3" value="62.4" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>All treated participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>All treated participants</population>
          <units>Count of participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <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>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period</title>
        <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
        <time_frame>From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period</title>
          <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
          <population>All treated participants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="4.4" upper_limit="23.4"/>
                    <measurement group_id="O2" value="11.5" lower_limit="4.4" upper_limit="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>DIFFERENCE IN INCIDENCE RATES</param_type>
            <param_value>0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.3</ci_lower_limit>
            <ci_upper_limit>12.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.30</ci_lower_limit>
            <ci_upper_limit>3.39</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period</title>
        <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
        <time_frame>From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period</title>
          <description>The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).</description>
          <population>All treated participants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="6.8"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>DIFFERENCE IN INCIDENCE RATES</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Participants With Drug Related Grade 3-5 Adverse Events</title>
        <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.</description>
        <time_frame>From first dose to 30 days after last dose of study therapy (up to approximately 48 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Participants With Drug Related Grade 3-5 Adverse Events</title>
          <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.</description>
          <population>All treated participants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1" lower_limit="34.0" upper_limit="62.4"/>
                    <measurement group_id="O2" value="42.3" lower_limit="28.7" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>DIFFERENCE IN INCIDENCE RATES</param_type>
            <param_value>5.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.3</ci_lower_limit>
            <ci_upper_limit>24.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.58</ci_lower_limit>
            <ci_upper_limit>2.78</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Participants With All Causality Grade 3-5 Adverse Events</title>
        <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria</description>
        <time_frame>From first dose to 30 days after last dose of study therapy (up to approximately 48 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Participants With All Causality Grade 3-5 Adverse Events</title>
          <description>The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria</description>
          <population>All treated participants</population>
          <units>Percentage of Particpants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.1" lower_limit="59.0" upper_limit="84.4"/>
                    <measurement group_id="O2" value="65.4" lower_limit="50.9" upper_limit="78.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>DIFFERENCE IN INCIDENCE RATES</param_type>
            <param_value>7.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.1</ci_lower_limit>
            <ci_upper_limit>25.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.42</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>3.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>All treated participants</population>
          <units>Percentage of Particpants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0" lower_limit="35.8" upper_limit="64.2"/>
                    <measurement group_id="O2" value="32.7" lower_limit="20.3" upper_limit="47.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)</description>
        <time_frame>From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)</time_frame>
        <population>All treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)</description>
          <population>All treated participants</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="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.06" lower_limit="9.92" upper_limit="18.23"/>
                    <measurement group_id="O2" value="7.69" lower_limit="3.42" upper_limit="11.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab</title>
        <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks</description>
        <time_frame>pre-dose on day 1 of cycle 2 and 4</time_frame>
        <population>All treated participants with available serum time-concentration data</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab</title>
          <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks</description>
          <population>All treated participants with available serum time-concentration data</population>
          <units>ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ipilimumab - Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.92" spread="28.9"/>
                    <measurement group_id="O2" value="3.43" spread="43.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ipilimumab - Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.90" spread="37.8"/>
                    <measurement group_id="O2" value="5.39" spread="39.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivolumab - Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.2" spread="29.1"/>
                    <measurement group_id="O2" value="16.1" spread="46.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivolumab - Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.5" spread="35.3"/>
                    <measurement group_id="O2" value="30.5" spread="43.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab</title>
        <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks</description>
        <time_frame>EOI on day 1 of cycle 1, 2, and 4</time_frame>
        <population>All treated participants with available serum time-concentration data</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Fixed Ratio Combination</title>
            <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Sequential Combination</title>
            <description>Nivolumab 3 mg/kg and ipilimumab&#xD;
1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab</title>
          <description>Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks</description>
          <population>All treated participants with available serum time-concentration data</population>
          <units>ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ipilimumab - Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.6" spread="23.7"/>
                    <measurement group_id="O2" value="13.4" spread="61.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ipilimumab - Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4" spread="24.8"/>
                    <measurement group_id="O2" value="15.6" spread="37.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ipilimumab - Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.9" spread="31.3"/>
                    <measurement group_id="O2" value="19.5" spread="38.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivolumab - Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.1" spread="22.4"/>
                    <measurement group_id="O2" value="60.7" spread="23.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivolumab - Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.6" spread="27.6"/>
                    <measurement group_id="O2" value="79.5" spread="71.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivolumab - Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.1" spread="30.1"/>
                    <measurement group_id="O2" value="88.9" spread="55.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A: Fixed Ratio Combination</title>
          <description>Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
        </group>
        <group group_id="E2">
          <title>Arm B: Sequential Combination</title>
          <description>Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>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="26" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Cardiomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenocortical insufficiency acute</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Biliary obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Drug-induced liver injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Achromobacter infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pelvic fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperglycaemic hyperosmolar nonketotic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Keratoacanthoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Peripheral sensorimotor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>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="49" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Eosinophilia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperchloraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephropathy toxic</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </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>Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Bristol-Myers Squibb Study Director</name_or_title>
      <organization>Bristol-Myers Squibb</organization>
      <phone>Please email</phone>
      <email>Clinical.Trials@bms.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/NCT03029780
org study id: CA209-800
nct id: NCT03029780
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate safety and efficacy of different administration
      regimens of nivolumab plus ipilimumab in subjects with renal cell carcinoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period
time frame: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)
description: The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).
measure: The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period
time frame: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)
description: The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).
measure: The Percentage of Participants With Drug Related Grade 3-5 Adverse Events
time frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)
description: The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.
measure: The Percentage of Participants With All Causality Grade 3-5 Adverse Events
time frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)
description: The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria
measure: Objective Response Rate (ORR)
time frame: From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)
description: The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Progression Free Survival (PFS)
time frame: From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)
description: The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)
measure: Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab
time frame: pre-dose on day 1 of cycle 2 and 4
description: Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks
measure: Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab
time frame: EOI on day 1 of cycle 1, 2, and 4
description: Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks
arm group label: Co-Administration
arm group type: Experimental
description: Nivolumab and Ipilimumab Co-Administration
arm group label: Sequential Administration
arm group type: Experimental
description: Nivolumab and Ipilimumab Sequential Administration
intervention type: Biological
intervention name: Opdivo
description: Specified dose on specified days
arm group label: Co-Administration
arm group label: Sequential Administration
other name: Nivolumab
intervention type: Biological
intervention name: Yervoy
description: Specified dose on specified days
arm group label: Co-Administration
arm group label: Sequential Administration
other name: Ipilimumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Chile
country: United States
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
url: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
description: FDA Safety Alerts and Recalls
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Nivolumab
mesh term: Ipilimumab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 