Nivolumab Plus Relatlimab or Ipilimumab in Metastatic Melanoma Stratified by MHC-II Expression

Exclusion Criteria

• •Patients with uveal melanoma.
• •Prior systemic anticancer therapy for unresectable or metastatic melanoma.
• •Prior treatment with LAG-3 targeted agents.
• •Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• •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, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation).
• •* 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 deep venous thrombosis, etc).
• •* Cardiovascular disease-related requirement for daily supplemental oxygen.
• •* History of two or more myocardial infarctions OR two or more coronary revascularization procedures.
• •* Subjects with history of myocarditis, regardless of etiology.
• •A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• •Participants with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease.
• •Subjects with active central nervous system (CNS) metastases, active brain metastases or leptomeningeal metastatic foci. For the subjects with brain metastases, if they are asymptomatic, they are eligible to participate in this study. If participants have received treatment for brain metastases and have no clinical evidence of progressive disease at least 1 week after completion of treatment for brain metastases and within 28 days prior to the first dose of protocol-indicated treatment on this study, they are eligible to participate in this study.
• •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• •Known history of hepatitis B or hepatitis C.
• •Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study or place the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study.
• •Subjects with life expectancy \< 6 months.
• •Subjects receiving any other investigational or standard antineoplastic agents.
• •Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• •Prisoners or participants who are involuntarily incarcerated.
• •Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
• •Psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant before registration in the trial.