Isunakinra Alone and in Combination With Pembrolizumab in Patients With Colorectal Cancer (MSS)

This study is testing a drug called isunakinra (alone or combined with the immunotherapy drug pembrolizumab) for people with a difficult-to-treat type of colorectal cancer. Specifically, this is for RAS-mutated, microsatellite-stable (MSS) colorectal cancer — a form that typically does not respond well to standard immunotherapy. Isunakinra works differently and may help overcome this resistance. **You may be eligible if...** - You have confirmed colorectal cancer with a RAS mutation and MSS/pMMR status, and a tumor mutation burden of 10 or more - Your cancer has measurable tumors on imaging - You have already received at least one prior treatment for metastatic disease with no good options remaining - Your organ function (kidneys, liver, blood counts) meets minimum thresholds - Your overall health status is good (ECOG 0–1) - You are able to use contraception if needed **You may NOT be eligible if...** - You are pregnant or breastfeeding - You have active autoimmune disease (with some exceptions) - You have active, uncontrolled brain metastases - You have a severe allergy to pembrolizumab or similar drugs - You are HIV positive - You have uncontrolled serious infections, heart problems, or psychiatric illness - You received another investigational treatment within the past 28 days Talk to your doctor to see if this trial is right for you.