REACTION (Radiation Enhanced Assessment of Combination Therapies in Immuno-ONcology) - Nivolumab or Nivolumab in Combination With Other Immuno-oncology (IO) Agents After Targeted Systemic Radiation in Patients With Advanced Esophagogastric Cancer

Exclusion Criteria

• •Any active or history of autoimmune disease (including any history of inflammatory bowel disease), or history of syndrome that required systemic steroids or immune-suppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy.
• •(Relatlimab arm only) Troponin T (TnT) or I (TnI) \> 2 × institutional upper limit of normal (ULN). Subjects with TnT or TnI levels between \> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤1 x ULN. If TnT or TnI levels are \> 1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the BMS Medical Monitor or designee. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the Bristol Myers Squibb (BMS) Medical Monitor or designee.
• •(Relatlimab arm only) Participants must not have a history of myocarditis
• •(Relatlimab arm only) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• •Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
• •Uncontrolled angina within the 3 months prior to consent
• •Any history of clinically significant arrhythmias (such as ventricular tachycardia, poorly controlled atrial fibrillation, ventricular fibrillation, or torsades de pointes)
• •Corrected QT interval (QTc) prolongation \> 480 msec
• •History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association (NYHA) functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, , poorly controlled venous thrombosis etc.)
• •Cardiovascular disease-related requirement for daily supplemental oxygen
• •History of two or more MIs OR two or more coronary revascularization procedures
• •(Relatlimab arm only) LVEF (Left Ventricular Ejection Fraction) assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration.
• •Ongoing requirement for systemic corticosteroids. However, inhalational steroids are allowed.
• •Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
• •Subjects with known brain metastasis are excluded from this study. Patients with suspected brain metastasis must have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
• •Subjects with a history of interstitial lung disease. Patients requiring continuous supplemental oxygen are excluded.
• •Use of any vaccines against infectious diseases (e.g., influenza, varicella. etc.) within 4 weeks (28 days) of initiation of study therapy.
• •Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
• •Known positive history or positive test for Human Immunodeficiency Virus or Acquired ImmunoDeficiency Syndrome (AIDS).
• •History of allergy to study drug components.
• •Women who are pregnant or nursing.
• •Men with female partners (WOCBP) that are not willing to use contraception
• •Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug or radiation hazardous or obscure the interpretation of toxicity or adverse events.
• •Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.