<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/NCT02966548</url>
  </required_header>
  <id_info>
    <org_study_id>CA224-034</org_study_id>
    <nct_id>NCT02966548</nct_id>
  </id_info>
  <brief_title>Safety Study of BMS-986016 With or Without Nivolumab in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1 Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ono Pharmaceutical Co. Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bristol-Myers Squibb</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be used to determine the safety and tolerability of BMS-986016 administered&#xD;
      alone and in combination with Nivolumab in subjects with advanced solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 4, 2017</start_date>
  <completion_date type="Anticipated">September 8, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 8, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events (AE)</measure>
    <time_frame>Approximately 2.2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of serious adverse events (SAE)</measure>
    <time_frame>Approximately 2.2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of deaths</measure>
    <time_frame>Approximately 2.2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of laboratory abnormalities</measure>
    <time_frame>Approximately 2.2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed serum concentration (Cmax) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed serum concentration (Tmax) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough observed serum concentration (Ctrough) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at the end of a dosing interval (Ctau) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total body clearance (CLT) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state (Vss) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective elimination half-life (T-HALFeff) that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation index; ration of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg) (DF) of BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response (BOR)</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of positive anti-drug antibody (ADA) to BMS-986016</measure>
    <time_frame>Cycle 1, 2, 3, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of positive anti-drug antibody (ADA) to Nivolumab</measure>
    <time_frame>Cycle 1, 2, 3, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relatlimab (BMS-986016) administered every 2 weeks as a single agent intravenous formulation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relatlimab (BMS-986016) will be administered in combination with Nivolumab every 2 weeks or every 4 weeks as an intravenous formulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Relatlimab</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_label>Monotherapy</arm_group_label>
    <other_name>BMS-986016</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>BMS-936558</other_name>
    <other_name>Opdivo</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;
          -  Must have histologic or cytologic confirmation of an incurable solid malignancy that&#xD;
             is advanced (metastatic and/or unresectable)&#xD;
&#xD;
          -  Must have received, and then progressed or been intolerant to, standard treatment&#xD;
             regimen in the advanced or metastatic setting, if such a therapy exists&#xD;
&#xD;
          -  Presence of at least one lesion with measurable disease as defined by RECIST v1.1&#xD;
             criteria for response assessment&#xD;
&#xD;
          -  Males and Females, ages 20 years or older, inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected CNS (central nervous system) metastases or with the CNS as the only&#xD;
             site of active disease&#xD;
&#xD;
          -  Other concomitant malignancies (with some exceptions per protocol)&#xD;
&#xD;
          -  Any active autoimmune disease or history of known or suspected autoimmune disease&#xD;
&#xD;
          -  History of uncontrolled or significant cardiovascular disease&#xD;
&#xD;
        Other protocol defined inclusion/exclusion criteria could apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 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>Local Institution - 0001</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Chiba</state>
        <zip>2778577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</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>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 1, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Relatlimab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02966548
org study id: CA224-034
nct id: NCT02966548
lead sponsor: 
collaborator: 
has dmc: Yes
This study will be used to determine the safety and tolerability of BMS-986016 administered
      alone and in combination with Nivolumab in subjects with advanced solid tumors.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events (AE)
time frame: Approximately 2.2 years
measure: Number of serious adverse events (SAE)
time frame: Approximately 2.2 years
measure: Number of deaths
time frame: Approximately 2.2 years
measure: Number of laboratory abnormalities
time frame: Approximately 2.2 years
measure: Maximum observed serum concentration (Cmax) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Time of maximum observed serum concentration (Tmax) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Trough observed serum concentration (Ctrough) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Concentration at the end of a dosing interval (Ctau) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Total body clearance (CLT) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Volume of distribution at steady state (Vss) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Effective elimination half-life (T-HALFeff) that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Accumulation index; ration of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg) (DF) of BMS-986016
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Best overall response (BOR)
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Duration of response (DOR)
time frame: Cycle 1, 2, 3, 4, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Frequency of positive anti-drug antibody (ADA) to BMS-986016
time frame: Cycle 1, 2, 3, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
measure: Frequency of positive anti-drug antibody (ADA) to Nivolumab
time frame: Cycle 1, 2, 3, 5, 9, 13, 17, 21 (28 days/cycle), 60-day follow-up, 135-day follow-up
arm group label: Monotherapy
arm group type: Experimental
description: Relatlimab (BMS-986016) administered every 2 weeks as a single agent intravenous formulation
arm group label: Combination Therapy
arm group type: Experimental
description: Relatlimab (BMS-986016) will be administered in combination with Nivolumab every 2 weeks or every 4 weeks as an intravenous formulation
intervention type: Drug
intervention name: Relatlimab
description: Specified dose on specified days
arm group label: Combination Therapy
arm group label: Monotherapy
other name: BMS-986016
intervention type: Drug
intervention name: Nivolumab
description: Specified dose on specified days
arm group label: Combination Therapy
other name: BMS-936558
other name: Opdivo
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
country: Japan
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
responsible party type: Sponsor
mesh term: Nivolumab
mesh term: Relatlimab