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

This trial tests immunotherapy drugs (cemiplimab, with or without fianlimab) as a non-surgical treatment option for older or medically frail patients with a specific type of colorectal cancer (MSI-H or dMMR — a type that tends to respond well to immunotherapy) that has not yet been treated. **You may be eligible if...** - You have localized or locally advanced colorectal cancer that is MSI-H or dMMR (a specific genetic marker — ask your doctor) - You have not received any prior treatment for this cancer - You are 70 or older (for Cohorts A and B), OR 18 or older and not a good surgical candidate or unwilling to have surgery (for Cohorts C and D) - You are willing to have regular surveillance scans and biopsies over 24 months - Your heart function and organ function meet the required levels **You may NOT be eligible if...** - You have previously received immunotherapy for any reason in the 5 years before your colorectal cancer diagnosis - You have active autoimmune disease - You are currently taking chronic steroids - You have had an organ transplant - You have low oxygen levels or are on home oxygen - You have uncontrolled infections or serious heart disease Talk to your doctor to see if this trial is right for you.