The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with microsatellite instability high (MSI-H) solid tumors refractory to prior PD-(L)1 therapy.

Inclusion Criteria:

• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Have metastatic or locally advanced mismatch repair deficient/MSI-H disease.
• Patients must have received prior PD-1/PD-L1 inhibitor therapy
• Patients with the presence of at least one measurable lesion.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented left ventricular ejection fraction (LVEF) ≥ 50% - 6 month prior to drug administration.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Known history or evidence of brain metastases.
• Require any antineoplastic therapy.
• History of prior treatment with anti-LAG3.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any investigational cytotoxic drug within 4 weeks prior to study treatment.
• Have received any investigational drugs, a live vaccine, any allergen hyposensitization therapy, growth factors or major surgery within 28 days prior to study treatment.
• Major surgery
• Hypersensitivity reaction to any monoclonal antibody.
• Has an active known or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Requires daily supplemental oxygen
• History of interstitial lung disease.
• Significant heart disease
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV or hepatitis B or C at screening.
• Has an active infection.
• Unable to have blood drawn.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prior life-threatening toxicity to anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4
• Woman who are pregnant or breastfeeding.