Nivolumab Plus Relatlimab in Patients With Metastatic Uveal Melanoma

Inclusion Criteria

• Have a biopsy-proven diagnosis of metastatic uveal melanoma, previously untreated with anti-PD-1,Cytotoxic T lymphocyte antigen 4 (CTLA-4) and/or lymphocyte activation gene 3 (LAG-3) blocking antibodies.
• Agree to undergo a pre-treatment and a post-treatment fresh biopsy of the tumor, if easily accessible and low-risk.
• Have completed all previous therapy for a minimum of 3 weeks before the first dose of experimental treatment. All adverse events of previous therapy must have resolved. Palliative radiation therapy to a limited field is allowed within this 3 week period.
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Left Ventricular Ejection Fraction (LVEF) assessment with documented LVEF 50% by either TTE or Multiple Gated Acquisition (MUGA) (TTE preferred test) within 6 months from first study drug administration
• Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 10 days of treatment initiation:
• Hematological:
• Absolute neutrophil count (ANC) ≥1, 500 /microliter (mcL)
• Platelets ≥100,000 / mcL
• Hemoglobin ≥ 9 g/dL or ≥5.6 mmol/L (within 7 days of assessment)
• Renal:
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR
• Measured or calculated a creatinine clearance ≥30 mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Hepatic:
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
• Aspartate Aminotransferase (AST) (SGOT) and Alanine Amino Transferase (ALT) (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• Coagulation:
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Creatinine clearance should be calculated per institutional standard.
• If a female of childbearing potential, have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• If a female of childbearing potential, be willing to use an adequate method of contraception as outlined in Section 5.8 Contraception, for the course of the study through 24 weeks after the last dose of study medication. Must abstain from ova donation for a minimum of 5 months after the end of treatment.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• If a male of childbearing potential, agree to use an adequate method of contraception as outlined in Section 5.8- Contraception, starting with the first dose of study therapy through 7 months after the last dose of study therapy. Must abstain from sperm donation for a minimum of 24 weeks after the end of treatment.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

• Are currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment.
• Have a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on replace