Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor

Eligibility 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.
• * 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.