Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer

This study is testing whether a combination of three targeted drugs — avutometinib, defactinib, and cetuximab — can treat advanced colorectal cancer that has stopped responding to anti-EGFR therapies (a standard treatment type for this cancer). **You may be eligible if...** - You have been diagnosed with advanced colorectal cancer that cannot be surgically removed - Your cancer has progressed on or is resistant to anti-EGFR therapy (such as cetuximab or panitumumab) - You have measurable tumors visible on imaging - You are able to provide informed consent and meet performance criteria **You may NOT be eligible if...** - You have BRAF-mutated colorectal cancer (unless a specific sub-group allows it) - You have significant heart problems or uncontrolled infections - You are pregnant or breastfeeding - You have received prior treatment with MEK, RAF, or FAK inhibitors Talk to your doctor to see if this trial is right for you.