Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer

Inclusion Criteria: * Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with KRASG12C mutation. KRASG12C on ctDNA may also be used as basis of eligibility, with approval from study or site PIs. * Unresectable or metastatic disease. * Previously treated with at least two prior chemotherapy regimens for metastatic disease (where a regimen is defined as a unique combination of 5-FU, oxaliplatin, irinotecan, bevacizumab (or biosimilar), capecitabine). A treatment with adjuvant therapy with progression within 6 months of completing therapy would be considered a prior chemotherapy regimen. * Presence of tumor lesions to be evaluated per RECIST 1.1patients must have measurable disease. * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of the proposed combination in patients \<18 years of age, and because solid tumor malignancies with KRASG12C mutation is rare among patients \< 18 years of age, children are excluded from this study. * Able to take oral medications. * Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose or five half-lives whichever is shorter. * Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and prior oxaliplatin-induced neuropathy). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Laboratory values…