xml: <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/NCT06029270</url>
    </required_header>
    <id_info>
      <org_study_id>NCI-2023-06678</org_study_id>
      <secondary_id>NCI-2023-06678</secondary_id>
      <secondary_id>NRG-HN011</secondary_id>
      <secondary_id>NRG-HN011</secondary_id>
      <secondary_id>U10CA180868</secondary_id>
      <nct_id>NCT06029270</nct_id>
    </id_info>
    <brief_title>Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer</brief_title>
    <official_title>A Randomized Phase II Study of Nivolumab Versus Nivolumab and BMS-986016 (Relatlimab) as Maintenance Treatment After First-Line Treatment With Platinum-Gemcitabine-Nivolumab for Patients With Epstein-Barr Virus-Associated Recurrent/Metastatic Nasopharyngeal Carcinoma (REMAIN)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Cancer Institute (NCI)</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy&#xD;
        after initial treatment for nasopharyngeal cancer that has come back after a period of&#xD;
        improvement (recurrent) or that has spread from where it first started (primary site) to&#xD;
        other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere&#xD;
        with the ability of tumor cells to grow and spread. The usual approach of treatment is&#xD;
        initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and&#xD;
        gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is&#xD;
        finished, patients may continue to receive additional immunotherapy. Carboplatin is in a&#xD;
        class of medications known as platinum-containing compounds. It works in a way similar to the&#xD;
        anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by&#xD;
        killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal&#xD;
        antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may&#xD;
        interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy&#xD;
        drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells.&#xD;
        Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend&#xD;
        the time without the tumor cells grow or spread longer than the usual approach in patients&#xD;
        with recurrent or metastatic nasopharyngeal cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance therapy shows a&#xD;
        signal of improved progression-free survival (PFS) according to Response Evaluation. Criteria&#xD;
        in Solid Tumors (RECIST) 1.1 in patients who do not progress following treatment with&#xD;
        platinum-gemcitabine-nivolumab combination in the first-line treatment of recurrent and/or&#xD;
        metastatic nasopharyngeal carcinoma (R/M NPC).&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves overall&#xD;
        survival (OS) compared to nivolumab maintenance alone.&#xD;
  &#xD;
        II. To compare patterns of failure (local-regional relapse and distant metastasis) between&#xD;
        treatment arms.&#xD;
  &#xD;
        III. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves&#xD;
        objective response, duration of response, and disease control rate compared to nivolumab&#xD;
        maintenance alone.&#xD;
  &#xD;
        IV. To evaluate the tolerability of nivolumab-BMS-986016 (relatlimab) maintenance and assess&#xD;
        and compare toxicity between arms based on the Common Terminology Criteria for Adverse Events&#xD;
        version 5.0 (CTCAE v5.0) criteria.&#xD;
  &#xD;
        V. To evaluate baseline plasma Epstein-Barr virus (EBV) DNA (&lt; 2000 copies/mL vs. &gt;= 2000&#xD;
        copies/mL) as a prognostic biomarker.&#xD;
  &#xD;
        VI. To validate post-induction plasma EBV DNA (detectable [&gt;= 1 copies/mL] vs. undetectable&#xD;
        [0 copies/mL]) as a prognostic biomarker.&#xD;
  &#xD;
        EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. To collect blood and tissue specimens for future translational science studies.&#xD;
  &#xD;
        II. To assess post-induction plasma EBV DNA (detectable [&gt;= 1 copies/mL] vs. undetectable [0&#xD;
        copies/mL]) as a predictive biomarker.&#xD;
  &#xD;
        OUTLINE:&#xD;
  &#xD;
        INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes, cisplatin&#xD;
        IV or carboplatin IV over 60 minutes on day 1 of each cycle and gemcitabine IV over 30&#xD;
        minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the&#xD;
        absence of disease progression or unacceptable toxicity. Patients undergo computed tomography&#xD;
        (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on&#xD;
        study.&#xD;
  &#xD;
        MAINTENANCE THERAPY: Patients who do not progress radiologically are randomized to 1 of 2&#xD;
        arms.&#xD;
  &#xD;
        ARM I: Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2&#xD;
        years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or&#xD;
        MRI on study. Patients also undergo positron emission tomography (PET)/CT or bone scan as&#xD;
        clinically indicated.&#xD;
  &#xD;
        ARM II: Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes.&#xD;
        Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or&#xD;
        bone scan as clinically indicated.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up every 4 months for 2&#xD;
        years,every 6 months for 5 years, and then annually.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 14, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2029</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2029</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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>Time from randomization to progressive disease (PD) or death due to any cause, assessed up to 6 years</time_frame>
      <description>Will be assessed in both treatment arms and will be estimated using the Kaplan-Meier method. The comparison of PFS distributions between treatment arms will be performed using the log-rank test. Additional analyses of treatment effect will be performed using Cox models with the stratification factors included as a fixed covariates, as well as other tumor and patient characteristics, listed below. Median PFS and the corresponding 95% confidence intervals (CIs) for each arm will be estimated with the Brookmeyer-Crowley method. Multivariable analysis will be performed using a Cox proportional hazards model and relevant patient and tumor characteristics (country [Asian sites versus (vs.) Non-Asian sites], keratinizing squamous carcinoma, gender, age, and baseline Epstein-Barr virus (EBV) deoxyribonucleic acid [DNA]). Hazard ratios and their respective 85% lower confidence bound, and 95% confidence intervals will be provided.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Time from randomization to death due to any cause, assessed up to 6 years</time_frame>
      <description>Will be estimated using the Kaplan-Meier method and between-arm differences will be assessed using the log-rank test. Median OS and the corresponding 95% CIs using log-log transformation to survival function for each arm will be estimated with the Brookmeyer-Crowley method.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tumor response</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Locoregional failure</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distant metastasis</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will be graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms using a chi-square test for proportions and confidence intervals for rate difference will be computed using Miettinen-Nurminen (score) method</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Post-induction plasma EBV DNA as a prognostic biomarker</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will be defined as a binary biomarker (detectable: &gt;= 1 copies/mL vs. undetectable: 0 copies/mL). Biomarker effect HRs from multivariable Cox models, including key tumor and patient characteristics will also be reported.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pre-induction plasma EBV DNA vs. progressive disease (PD) during induction treatment</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will include all patients treated with concurrent (induction) treatment and a binary biomarker based on pre-induction plasma EBV DNA (&lt; 2000 vs. ≥2000 copies/mL). PD rates during induction for each biomarker subgroup will be computed assuming a binomial distribution and compared between biomarker subgroups using a chi-square test. Multivariable Cox models, including key tumor and patient characteristics will also be included.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Persistent plasma EBV DNA vs. PFS</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will examine the association between persistent EBV DNA after induction treatment and PFS. Only randomized patients with positive pre-induction plasma EBV DNA will be included (~90-95%). Patients will be classified into &quot;EBV DNA positive to negative&quot; and &quot;EBV DNA consistently positive&quot; based on the pre-induction and post-induction EBV DNA. Multivariable Cox models, including key tumor and patient characteristics will also be included.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Post-induction EBV DNA as a predictive biomarker</measure>
      <time_frame>Up to 6 years</time_frame>
      <description>Will be assessed of the predictive role of post-induction EBV DNA on on PFS and OS will be performed using the binary biomarker. Cox proportional hazards model with treatment arm, binary biomarker, and its interaction will be used for these analyses. Treatment effect hazard ratios and 95% confidence intervals will be reported. Adjusted HR estimates will be obtained after adding key patient and tumor characteristics.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">156</enrollment>
    <condition>Nasopharyngeal Carcinoma</condition>
    <arm_group>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive nivolumab IV over 30 minutes, cisplatin IV or carboplatin IV over 60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection during screening and on study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Scan</intervention_name>
      <description>Undergo bone scan</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <other_name>Bone Scintigraphy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>Blastocarb</other_name>
      <other_name>Carboplat</other_name>
      <other_name>Carboplatin Hexal</other_name>
      <other_name>Carboplatino</other_name>
      <other_name>Carboplatinum</other_name>
      <other_name>Carbosin</other_name>
      <other_name>Carbosol</other_name>
      <other_name>Carbotec</other_name>
      <other_name>CBDCA</other_name>
      <other_name>Displata</other_name>
      <other_name>Ercar</other_name>
      <other_name>JM-8</other_name>
      <other_name>JM8</other_name>
      <other_name>Nealorin</other_name>
      <other_name>Novoplatinum</other_name>
      <other_name>Paraplatin</other_name>
      <other_name>Paraplatin AQ</other_name>
      <other_name>Paraplatine</other_name>
      <other_name>Platinwas</other_name>
      <other_name>Ribocarbo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cisplatin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>Abiplatin</other_name>
      <other_name>Blastolem</other_name>
      <other_name>Briplatin</other_name>
      <other_name>CDDP</other_name>
      <other_name>Cis-diammine-dichloroplatinum</other_name>
      <other_name>Cis-diamminedichloridoplatinum</other_name>
      <other_name>Cis-diamminedichloro Platinum (II)</other_name>
      <other_name>Cis-diamminedichloroplatinum</other_name>
      <other_name>Cis-dichloroammine Platinum (II)</other_name>
      <other_name>Cis-platinous Diamine Dichloride</other_name>
      <other_name>Cis-platinum</other_name>
      <other_name>Cis-platinum II</other_name>
      <other_name>Cis-platinum II Diamine Dichloride</other_name>
      <other_name>Cismaplat</other_name>
      <other_name>Cisplatina</other_name>
      <other_name>Cisplatinum</other_name>
      <other_name>Cisplatyl</other_name>
      <other_name>Citoplatino</other_name>
      <other_name>Citosin</other_name>
      <other_name>Cysplatyna</other_name>
      <other_name>DDP</other_name>
      <other_name>Lederplatin</other_name>
      <other_name>Metaplatin</other_name>
      <other_name>Neoplatin</other_name>
      <other_name>Peyrone's Chloride</other_name>
      <other_name>Peyrone's Salt</other_name>
      <other_name>Placis</other_name>
      <other_name>Plastistil</other_name>
      <other_name>Platamine</other_name>
      <other_name>Platiblastin</other_name>
      <other_name>Platiblastin-S</other_name>
      <other_name>Platinex</other_name>
      <other_name>Platinol</other_name>
      <other_name>Platinol- AQ</other_name>
      <other_name>Platinol-AQ</other_name>
      <other_name>Platinol-AQ VHA Plus</other_name>
      <other_name>Platinoxan</other_name>
      <other_name>Platinum</other_name>
      <other_name>Platinum Diamminodichloride</other_name>
      <other_name>Platiran</other_name>
      <other_name>Platistin</other_name>
      <other_name>Platosin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT or PET/CT</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>dFdC</other_name>
      <other_name>dFdCyd</other_name>
      <other_name>Difluorodeoxycytidine</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo MRI</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>Magnetic Resonance</other_name>
      <other_name>Magnetic resonance imaging (procedure)</other_name>
      <other_name>Magnetic Resonance Imaging Scan</other_name>
      <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
      <other_name>MR</other_name>
      <other_name>MR Imaging</other_name>
      <other_name>MRI</other_name>
      <other_name>MRI Scan</other_name>
      <other_name>NMR Imaging</other_name>
      <other_name>NMRI</other_name>
      <other_name>Nuclear Magnetic Resonance Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Nivolumab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <arm_group_label>Induction therapy (Platinum-gemcitabine-nivolumab)</arm_group_label>
      <other_name>ABP 206</other_name>
      <other_name>BMS-936558</other_name>
      <other_name>CMAB819</other_name>
      <other_name>MDX-1106</other_name>
      <other_name>NIVO</other_name>
      <other_name>Nivolumab Biosimilar ABP 206</other_name>
      <other_name>Nivolumab Biosimilar CMAB819</other_name>
      <other_name>ONO-4538</other_name>
      <other_name>Opdivo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Positron Emission Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Arm I (Nivolumab)</arm_group_label>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <other_name>Medical Imaging, Positron Emission Tomography</other_name>
      <other_name>PET</other_name>
      <other_name>PET Scan</other_name>
      <other_name>Positron emission tomography (procedure)</other_name>
      <other_name>Positron Emission Tomography Scan</other_name>
      <other_name>Positron-Emission Tomography</other_name>
      <other_name>proton magnetic resonance spectroscopic imaging</other_name>
      <other_name>PT</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Relatlimab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Arm II (Nivolumab, relatlimab)</arm_group_label>
      <other_name>BMS-986016</other_name>
      <other_name>BMS986016</other_name>
      <other_name>Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  PRIOR TO STEP 1 REGISTRATION:&#xD;
  &#xD;
            -  Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal&#xD;
               carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites.&#xD;
               Patients who present with metastatic disease (de novo) at diagnosis are also eligible.&#xD;
               For locoregional recurrence, the disease must not be amenable to potentially curative&#xD;
               surgery or re-irradiation. Eligible patient must have the following characteristics:&#xD;
  &#xD;
                 -  Tumor showing (histological/cytological) Epstein-Barr encoded ribonucleic acid&#xD;
                    (EBER)-positivity (e.g., In situ hybridization, immunohistochemistry) or&#xD;
  &#xD;
                 -  A known history of detectable plasma EBV DNA (via a polymerase chain reaction&#xD;
                    [PCR]-based assay) at any time point since the initial diagnosis of NPC.&#xD;
  &#xD;
            -  Measurable disease as defined by RECIST 1.1 criteria. Lesion(s) that have been&#xD;
               irradiated previously can be counted as measurable as long as radiological progression&#xD;
               after the prior radiation therapy has been demonstrated.&#xD;
  &#xD;
                 -  Contrast enhanced CT scan of the chest. The contrast enhanced CT component of a&#xD;
                    whole-body PET-CT is also acceptable. The plain (non-contrast) CT component of a&#xD;
                    PET-CT is not acceptable.&#xD;
  &#xD;
                 -  CT the abdomen and pelvis, if clinically indicated (diagnostic quality with&#xD;
                    contrast, unless contraindicated).&#xD;
  &#xD;
                 -  Patients with known locoregional disease must have contrast enhanced MRI or CT of&#xD;
                    the nasopharynx and neck as this disease site(s) may be assessed as target&#xD;
                    lesions. For patients without known locoregional disease, imaging of the&#xD;
                    nasopharynx and neck is optional.&#xD;
  &#xD;
                 -  Symptomatic and active brain metastases and/or leptomeningeal metastasis on CT&#xD;
                    and/or MRI imaging: Patients who have prior therapies for brain and&#xD;
                    leptomeningeal metastasis or cord/cauda compression who are clinically stable for&#xD;
                    &gt;= 2 months prior to registration and have discontinued systemic steroids therapy&#xD;
                    (&gt; 10 mg/day prednisone or equivalent) &gt; 4 weeks prior to registration are&#xD;
                    eligible.&#xD;
  &#xD;
                 -  Patients with base of skull involvement by NPC are allowed unless their disease&#xD;
                    is directly invading the brain parenchyma, associated with clinical symptoms&#xD;
                    and/or significant vasogenic edema on radiological imaging.&#xD;
  &#xD;
            -  Age &gt;= 18 years.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2.&#xD;
  &#xD;
            -  Negative urine or serum pregnancy test (in persons of childbearing potential) within&#xD;
               14 days prior to registration. Childbearing potential is defined as any person who has&#xD;
               experienced menarche and who has not undergone surgical sterilization (hysterectomy or&#xD;
               bilateral oophorectomy) or who is not postmenopausal.&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &gt;= 1500 cells/mm^3&#xD;
  &#xD;
            -  Platelets &gt;= 100,000 cells/mm^3.&#xD;
  &#xD;
            -  Hemoglobin (Hgb) &gt;= 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not&#xD;
               accepted.).&#xD;
  &#xD;
            -  Total bilirubin =&lt;1.5 × institutional upper limit of normal (ULN) or direct bilirubin&#xD;
               =&lt; ULN for patients with total bilirubin levels &gt; 1.5 × ULN. Patients with known&#xD;
               Gilbert's disease who have serum bilirubin level =&lt; 3 × ULN may be enrolled.&#xD;
  &#xD;
            -  Alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =&lt; 3 × ULN (=&lt;&#xD;
               5 × ULN for patients with liver metastases).&#xD;
  &#xD;
            -  Serum creatinine or calculated creatinine clearance (CrCl) based on Cockcroft-Gault&#xD;
               equation =&lt; 1.5× ULN or &gt; 30 mL/min for patients with serum creatinine levels &gt; 1.5 ×&#xD;
               ULN. Cisplatin or carboplatin may be used at the discretion of the investigator -&#xD;
               except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be&#xD;
               used instead of cisplatin. CrCl must be &gt; 50 mL/min for cisplatin to be used.&#xD;
  &#xD;
            -  Albumin-adjusted calcium level based on corrected calcium equation =&lt; 1.5× ULN&#xD;
               (patients are allowed to have treatment for hypercalcemia prior to starting&#xD;
               treatment).&#xD;
  &#xD;
            -  No prior systemic treatment for recurrent/metastatic (R/M) NPC including cytotoxic&#xD;
               chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed.&#xD;
  &#xD;
            -  No prior treatment with a PD-1 inhibitor (except if given as adjuvant or neoadjuvant&#xD;
               therapy for NPC), PD-L1 inhibitor, anti-PD-L2 inhibitor, LAG-3 inhibitor, CTLA-4&#xD;
               inhibitor (except if given as adjuvant or neoadjuvant therapy for non-recurrent and&#xD;
               non-metastatic NPC), or any other antibody or drug specifically targeting T-cell&#xD;
               co-stimulation or immune checkpoint pathways.&#xD;
  &#xD;
            -  The interval between the last dose of curative-intent treatment for non-recurrent,&#xD;
               non-metastatic NPC, including definitive radiotherapy (RT) and/or induction,&#xD;
               concurrent, or adjuvant chemotherapy and recurrence must be ˃ 6 months.&#xD;
  &#xD;
            -  Clinically significant toxicities from any prior systemic therapy or radiotherapy must&#xD;
               have resolved to grade 0 or 1 as per NCI CTCAE v 5.0 - except alopecia, dry mouth,&#xD;
               dysgeusia, dysphagia, and fatigue. Patients with a history of grade 3-4 cisplatin&#xD;
               related neuropathy must have recovered to grade 0-2 prior to registration. Patients&#xD;
               with a history of hearing impairment, or ototoxicity from prior cisplatin, of any&#xD;
               grade are allowed.&#xD;
  &#xD;
            -  No prior palliative RT within 30 days prior to registration. This includes RT given&#xD;
               with palliative intent to recurrent/metastatic sites. The irradiated sites must not be&#xD;
               the only sites of measurable recurrent disease.&#xD;
  &#xD;
            -  No major surgical procedures within 30 days prior to registration.&#xD;
  &#xD;
            -  No history of unstable angina requiring hospitalization within the last 6 months.&#xD;
  &#xD;
            -  No history of myocardial infarction within the last 6 months.&#xD;
  &#xD;
            -  New York Heart Association Functional Classification II or better (NYHA Functional&#xD;
               Classification III/IV are not eligible). Patients with symptomatic coronary artery&#xD;
               disease, congestive heart failure or a known history of having a left ventricular&#xD;
               ejection fraction &lt; 50% must be stably controlled with medication in the opinion of&#xD;
               the treating physician, in consultation with a cardiologist if appropriate.&#xD;
  &#xD;
            -  No prior history of myocarditis.&#xD;
  &#xD;
            -  No active infection requiring IV antibiotics, IV antiviral, or IV antifungal&#xD;
               treatments at the time of study registration.&#xD;
  &#xD;
            -  No history of (non-infectious) pneumonitis that required steroids or current&#xD;
               pneumonitis requiring steroids and/or immunosuppressive therapy, idiopathic pulmonary&#xD;
               fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis&#xD;
               obliterans), or idiopathic pneumonitis.&#xD;
  &#xD;
            -  No history of multi-drug resistant mycobacterium tuberculosis (TB) or active TB, as&#xD;
               defined by systemic treatment received =&lt; 2 years prior to registration. Note:&#xD;
               Patients who had a history of treated TB ˃ 2 years prior to registration are allowed.&#xD;
  &#xD;
            -  No prior solid organ transplant or bone marrow transplant.&#xD;
  &#xD;
            -  No conditions requiring systemic treatment with either immunosuppressive doses of&#xD;
               corticosteroids (&gt; 10 mg daily prednisone or equivalents) or other immunosuppressive&#xD;
               medications within 14 days of registration. Inhaled or topical steroids and adrenal&#xD;
               replacement doses &lt; 10 mg daily prednisone equivalents are permitted in the absence of&#xD;
               active autoimmune disease. Steroid premedication for the prophylaxis of CT&#xD;
               contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic&#xD;
               premedication prior to chemotherapy is also allowed.&#xD;
  &#xD;
            -  No active autoimmune disease requiring systemic treatment (i.e., disease modifying&#xD;
               agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These&#xD;
               may include (but not limited to) patients with a history of immune-related neurologic&#xD;
               disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre&#xD;
               syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, rheumatoid&#xD;
               arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD),&#xD;
               Crohn's disease, ulcerative colitis, autoimmune hepatitis, glomerulonephritis; and&#xD;
               patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome,&#xD;
               or phospholipid syndrome.&#xD;
  &#xD;
                 -  Note: Patients are permitted to enroll if they have vitiligo; type I diabetes&#xD;
                    mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only&#xD;
                    hormone replacement; alopecia; and/or psoriasis not requiring systemic treatment.&#xD;
                    Conditions not expected to recur in the absence of an external trigger are&#xD;
                    permitted to enroll.&#xD;
  &#xD;
            -  No prior live vaccine within 30 days prior to registration. Examples of live vaccines&#xD;
               include, but are not limited to, the following: measles, mumps, rubella,&#xD;
               varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza&#xD;
               vaccines for injection are generally killed virus vaccines and are allowed; however,&#xD;
               intranasal influenza vaccines (e.g., FluMist registered trade mark) are live&#xD;
               attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines&#xD;
               that are approved by the local drug regulatory authority of the participating region&#xD;
               are allowed.&#xD;
  &#xD;
            -  No known history of grade 3-4 allergic reaction or hypersensitivity reaction to&#xD;
               cisplatin, carboplatin, or gemcitabine.&#xD;
  &#xD;
            -  No known history of grade 4 hypersensitivity (or infusion) reaction to any monoclonal&#xD;
               antibody. Patients who had prior grade 3 hypersensitivity (or infusion) reaction but&#xD;
               could tolerate resumption of the antibody treatment after appropriate pre-medication&#xD;
               are eligible.&#xD;
  &#xD;
            -  PRIOR TO STEP 2 REGISTRATION:&#xD;
  &#xD;
            -  Collection of plasma EBV DNA at baseline is mandatory for all patients prior to Step 2&#xD;
               registration and induction treatment.&#xD;
  &#xD;
                 -  Note: Submission of the baseline sample will be batch shipped.&#xD;
  &#xD;
            -  PRIOR TO STEP 3 REGISTRATION/RANDOMIZATION: PATIENTS WITHOUT PROGRESSIVE DISEASE (PD)&#xD;
               ONLY:&#xD;
  &#xD;
            -  All patients must have received minimum of 3 cycles, and up to a maximum of 6 cycles&#xD;
               of induction treatment within 20 weeks from cycle 1, day 1 of induction treatment&#xD;
               (i.e., patients must have completed all induction treatment within 20 weeks from cycle&#xD;
               1 day 1, including the treatment breaks). Patients must have completed 6 cycles of&#xD;
               induction treatment, except in the following circumstances:&#xD;
  &#xD;
                 -  Significant dose delays as a result of treatment-related toxicities.&#xD;
  &#xD;
                 -  Intercurrent illness(s), that rendered the patient unable to continue induction&#xD;
                    treatment.&#xD;
  &#xD;
                 -  Note: If a patient received &lt; 6 cycles of induction treatment for reasons other&#xD;
                    than the above circumstances, they will not be eligible for randomization.&#xD;
  &#xD;
            -  A CT scan within 30 days prior to Step 3 registration/randomization is required. If&#xD;
               the most recent scan performed is not within this time frame, a repeat scan is&#xD;
               required to assess response.&#xD;
  &#xD;
            -  Did not meet any criteria that result in permanent discontinuation of study treatment&#xD;
               during induction treatment phase.&#xD;
  &#xD;
            -  Must meet the criteria for starting/resuming a new cycle of maintenance treatment.&#xD;
  &#xD;
            -  Did not experience any nivolumab-related autoimmune toxicities that would result in&#xD;
               permanent discontinuation of nivolumab during the induction treatment phase.&#xD;
  &#xD;
            -  Collection of the plasma EBV DNA post-induction treatment is mandatory.&#xD;
  &#xD;
                 -  Note: Submission of the post-induction sample will be batch shipped.&#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>Brigette B Ma</last_name>
      <role>Principal Investigator</role>
      <affiliation>NRG Oncology</affiliation>
    </overall_official>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</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>Nasopharyngeal Carcinoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cisplatin</mesh_term>
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Nivolumab</mesh_term>
      <mesh_term>Relatlimab</mesh_term>
      <mesh_term>Immunoglobulins</mesh_term>
      <mesh_term>Immunoglobulin G</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>&quot;NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.&quot;</ipd_description>
      <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06029270
  org study id: NCI-2023-06678
  secondary id: NCI-2023-06678
  secondary id: NRG-HN011
  secondary id: NRG-HN011
  secondary id: U10CA180868
  nct id: NCT06029270
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy
        after initial treatment for nasopharyngeal cancer that has come back after a period of
        improvement (recurrent) or that has spread from where it first started (primary site) to
        other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere
        with the ability of tumor cells to grow and spread. The usual approach of treatment is
        initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and
        gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is
        finished, patients may continue to receive additional immunotherapy. Carboplatin is in a
        class of medications known as platinum-containing compounds. It works in a way similar to the
        anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by
        killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal
        antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may
        interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy
        drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells.
        Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend
        the time without the tumor cells grow or spread longer than the usual approach in patients
        with recurrent or metastatic nasopharyngeal cancer.
  PRIMARY OBJECTIVE:
  
        I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance therapy shows a
        signal of improved progression-free survival (PFS) according to Response Evaluation. Criteria
        in Solid Tumors (RECIST) 1.1 in patients who do not progress following treatment with
        platinum-gemcitabine-nivolumab combination in the first-line treatment of recurrent and/or
        metastatic nasopharyngeal carcinoma (R/M NPC).
  
        SECONDARY OBJECTIVES:
  
        I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves overall
        survival (OS) compared to nivolumab maintenance alone.
  
        II. To compare patterns of failure (local-regional relapse and distant metastasis) between
        treatment arms.
  
        III. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves
        objective response, duration of response, and disease control rate compared to nivolumab
        maintenance alone.
  
        IV. To evaluate the tolerability of nivolumab-BMS-986016 (relatlimab) maintenance and assess
        and compare toxicity between arms based on the Common Terminology Criteria for Adverse Events
        version 5.0 (CTCAE v5.0) criteria.
  
        V. To evaluate baseline plasma Epstein-Barr virus (EBV) DNA (< 2000 copies/mL vs. >= 2000
        copies/mL) as a prognostic biomarker.
  
        VI. To validate post-induction plasma EBV DNA (detectable [>= 1 copies/mL] vs. undetectable
        [0 copies/mL]) as a prognostic biomarker.
  
        EXPLORATORY OBJECTIVES:
  
        I. To collect blood and tissue specimens for future translational science studies.
  
        II. To assess post-induction plasma EBV DNA (detectable [>= 1 copies/mL] vs. undetectable [0
        copies/mL]) as a predictive biomarker.
  
        OUTLINE:
  
        INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes, cisplatin
        IV or carboplatin IV over 60 minutes on day 1 of each cycle and gemcitabine IV over 30
        minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the
        absence of disease progression or unacceptable toxicity. Patients undergo computed tomography
        (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on
        study.
  
        MAINTENANCE THERAPY: Patients who do not progress radiologically are randomized to 1 of 2
        arms.
  
        ARM I: Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2
        years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or
        MRI on study. Patients also undergo positron emission tomography (PET)/CT or bone scan as
        clinically indicated.
  
        ARM II: Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes.
        Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or
        unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or
        bone scan as clinically indicated.
  
        After completion of study treatment, patients are followed up every 4 months for 2
        years,every 6 months for 5 years, and then annually.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival (PFS)
  time frame: Time from randomization to progressive disease (PD) or death due to any cause, assessed up to 6 years
  description: Will be assessed in both treatment arms and will be estimated using the Kaplan-Meier method. The comparison of PFS distributions between treatment arms will be performed using the log-rank test. Additional analyses of treatment effect will be performed using Cox models with the stratification factors included as a fixed covariates, as well as other tumor and patient characteristics, listed below. Median PFS and the corresponding 95% confidence intervals (CIs) for each arm will be estimated with the Brookmeyer-Crowley method. Multivariable analysis will be performed using a Cox proportional hazards model and relevant patient and tumor characteristics (country [Asian sites versus (vs.) Non-Asian sites], keratinizing squamous carcinoma, gender, age, and baseline Epstein-Barr virus (EBV) deoxyribonucleic acid [DNA]). Hazard ratios and their respective 85% lower confidence bound, and 95% confidence intervals will be provided.
  measure: Overall survival (OS)
  time frame: Time from randomization to death due to any cause, assessed up to 6 years
  description: Will be estimated using the Kaplan-Meier method and between-arm differences will be assessed using the log-rank test. Median OS and the corresponding 95% CIs using log-log transformation to survival function for each arm will be estimated with the Brookmeyer-Crowley method.
  measure: Tumor response
  time frame: Up to 6 years
  description: Will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
  measure: Locoregional failure
  time frame: Up to 6 years
  description: Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
  measure: Distant metastasis
  time frame: Up to 6 years
  description: Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
  measure: Incidence of adverse events
  time frame: Up to 6 years
  description: Will be graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms using a chi-square test for proportions and confidence intervals for rate difference will be computed using Miettinen-Nurminen (score) method
  measure: Post-induction plasma EBV DNA as a prognostic biomarker
  time frame: Up to 6 years
  description: Will be defined as a binary biomarker (detectable: >= 1 copies/mL vs. undetectable: 0 copies/mL). Biomarker effect HRs from multivariable Cox models, including key tumor and patient characteristics will also be reported.
  measure: Pre-induction plasma EBV DNA vs. progressive disease (PD) during induction treatment
  time frame: Up to 6 years
  description: Will include all patients treated with concurrent (induction) treatment and a binary biomarker based on pre-induction plasma EBV DNA (< 2000 vs. ≥2000 copies/mL). PD rates during induction for each biomarker subgroup will be computed assuming a binomial distribution and compared between biomarker subgroups using a chi-square test. Multivariable Cox models, including key tumor and patient characteristics will also be included.
  measure: Persistent plasma EBV DNA vs. PFS
  time frame: Up to 6 years
  description: Will examine the association between persistent EBV DNA after induction treatment and PFS. Only randomized patients with positive pre-induction plasma EBV DNA will be included (~90-95%). Patients will be classified into "EBV DNA positive to negative" and "EBV DNA consistently positive" based on the pre-induction and post-induction EBV DNA. Multivariable Cox models, including key tumor and patient characteristics will also be included.
  measure: Post-induction EBV DNA as a predictive biomarker
  time frame: Up to 6 years
  description: Will be assessed of the predictive role of post-induction EBV DNA on on PFS and OS will be performed using the binary biomarker. Cox proportional hazards model with treatment arm, binary biomarker, and its interaction will be used for these analyses. Treatment effect hazard ratios and 95% confidence intervals will be reported. Adjusted HR estimates will be obtained after adding key patient and tumor characteristics.
  arm group label: Arm I (Nivolumab)
  arm group type: Active Comparator
  description: Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.
  arm group label: Arm II (Nivolumab, relatlimab)
  arm group type: Experimental
  description: Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  arm group type: Experimental
  description: Patients receive nivolumab IV over 30 minutes, cisplatin IV or carboplatin IV over 60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection during screening and on study.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Bone Scan
  description: Undergo bone scan
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  other name: Bone Scintigraphy
  intervention type: Drug
  intervention name: Carboplatin
  description: Given IV
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: Blastocarb
  other name: Carboplat
  other name: Carboplatin Hexal
  other name: Carboplatino
  other name: Carboplatinum
  other name: Carbosin
  other name: Carbosol
  other name: Carbotec
  other name: CBDCA
  other name: Displata
  other name: Ercar
  other name: JM-8
  other name: JM8
  other name: Nealorin
  other name: Novoplatinum
  other name: Paraplatin
  other name: Paraplatin AQ
  other name: Paraplatine
  other name: Platinwas
  other name: Ribocarbo
  intervention type: Drug
  intervention name: Cisplatin
  description: Given IV
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: Abiplatin
  other name: Blastolem
  other name: Briplatin
  other name: CDDP
  other name: Cis-diammine-dichloroplatinum
  other name: Cis-diamminedichloridoplatinum
  other name: Cis-diamminedichloro Platinum (II)
  other name: Cis-diamminedichloroplatinum
  other name: Cis-dichloroammine Platinum (II)
  other name: Cis-platinous Diamine Dichloride
  other name: Cis-platinum
  other name: Cis-platinum II
  other name: Cis-platinum II Diamine Dichloride
  other name: Cismaplat
  other name: Cisplatina
  other name: Cisplatinum
  other name: Cisplatyl
  other name: Citoplatino
  other name: Citosin
  other name: Cysplatyna
  other name: DDP
  other name: Lederplatin
  other name: Metaplatin
  other name: Neoplatin
  other name: Peyrone's Chloride
  other name: Peyrone's Salt
  other name: Placis
  other name: Plastistil
  other name: Platamine
  other name: Platiblastin
  other name: Platiblastin-S
  other name: Platinex
  other name: Platinol
  other name: Platinol- AQ
  other name: Platinol-AQ
  other name: Platinol-AQ VHA Plus
  other name: Platinoxan
  other name: Platinum
  other name: Platinum Diamminodichloride
  other name: Platiran
  other name: Platistin
  other name: Platosin
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT or PET/CT
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Gemcitabine
  description: Given IV
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: dFdC
  other name: dFdCyd
  other name: Difluorodeoxycytidine
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo MRI
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: Magnetic Resonance
  other name: Magnetic resonance imaging (procedure)
  other name: Magnetic Resonance Imaging Scan
  other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  other name: MR
  other name: MR Imaging
  other name: MRI
  other name: MRI Scan
  other name: NMR Imaging
  other name: NMRI
  other name: Nuclear Magnetic Resonance Imaging
  intervention type: Biological
  intervention name: Nivolumab
  description: Given IV
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  arm group label: Induction therapy (Platinum-gemcitabine-nivolumab)
  other name: ABP 206
  other name: BMS-936558
  other name: CMAB819
  other name: MDX-1106
  other name: NIVO
  other name: Nivolumab Biosimilar ABP 206
  other name: Nivolumab Biosimilar CMAB819
  other name: ONO-4538
  other name: Opdivo
  intervention type: Procedure
  intervention name: Positron Emission Tomography
  description: Undergo PET/CT
  arm group label: Arm I (Nivolumab)
  arm group label: Arm II (Nivolumab, relatlimab)
  other name: Medical Imaging, Positron Emission Tomography
  other name: PET
  other name: PET Scan
  other name: Positron emission tomography (procedure)
  other name: Positron Emission Tomography Scan
  other name: Positron-Emission Tomography
  other name: proton magnetic resonance spectroscopic imaging
  other name: PT
  intervention type: Biological
  intervention name: Relatlimab
  description: Given IV
  arm group label: Arm II (Nivolumab, relatlimab)
  other name: BMS-986016
  other name: BMS986016
  other name: Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Brigette B Ma
  role: Principal Investigator
  affiliation: NRG Oncology
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Nasopharyngeal Carcinoma
  mesh term: Cisplatin
  mesh term: Carboplatin
  mesh term: Gemcitabine
  mesh term: Nivolumab
  mesh term: Relatlimab
  mesh term: Immunoglobulins
  mesh term: Immunoglobulin G
  sharing ipd: Yes
  ipd description: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."
  ipd url: https://grants.nih.gov/policy/sharing.htm