Cemiplimab With or Without Fianlimab to Treat Older Patients With Localized or Locally Advanced MSI-H Colorectal Cancer

Inclusion Criteria for Cohort A and B: * Age ≥70 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0 -2 * Have histologically proven localized or locally advanced mismatch repair deficient (dMMR) or microsatellite unstable (MSI-H) colorectal cancer. * Must not have received any prior systemic treatment or radiation. * Must be agreeable to endoscopic, and CT surveillance for a total of 24 months. * Patient's acceptance to have a tumor biopsy. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures. * LVEF assessment with documented LVEF ≥ 45% by either TTE or MUGA (TTE preferred) within 6 months from first study drug administration. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. Inclusion Criteria for Cohort C and D: * Age ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0 -3. * Have histologically proven localized or locally advanced mismatch repair deficient (dMMR) or microsatellite unstable (MSI-H) colorectal cancer. * Patient deemed a poor surgical candidate after evaluation by a surgeon or unwilling to undergo surgery. * Must not have received any prior systemic treatment or radiation. * Must be agreeable to endoscopic, and CT surveillance for a total of 24 months. * Patient's acceptance to have a tumor biopsy. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria for Cohorts A and B: * Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug. * Have expected to require any other form of systemic or localized antineoplastic therapy while on study. * Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.). * History of prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies for any reason in the 5 years proceeding their colorectal cancer diagnosis. * Currently using any chronic systemic steroids. * Patient has received a live vaccine within 30 days of the first dose of study drug. * History of severe hypersensitivity reaction to any monoclonal antibody. * Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements. * Active autoimmune disease. * Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. * Patient has a pulse oximetry of \<92% on room air. * Patient is on supplemental home oxygen. * Has clinically significant heart disease. * Cohort B Only: Troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline. * Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures. * Unwilling or unable to follow the study schedule for any reason Exclusion for Cohort C and D: * Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug. * Have expected to require any other form of systemic or localized antineoplastic therapy while on study. * Currently using any chronic systemic steroids. * Patient has received a live vaccine within 30 days of the first dose of study drug. * History of severe hypersensitivity reaction to any monoclonal antibody. * Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. * Patient is pregnant or breastfeeding. * Cohort D Only: Troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline. * Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures. * Participation deemed not in the best interest of the patient. * Unwilling or unable to follow the study schedule for any reason.