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

Primary objectives: * To determine the optimal biological dose (OBD) of MRTX849 when used in combination with cetuximab and irinotecan. * To evaluate the safety profile of this combination. * To determine the antitumor activity of this combination in patients with metastatic KRASG12C colorectal cancer. Exploratory objectives: * To explore correlations between MRTX849 exposure and patient outcomes such as disease response, objective response rate (ORR), duration or response (DOR), progression-free survival (PFS), overall survival (OS), safety, and pharmacodynamic endpoints. * To evaluate the utility of detecting KRASG12C mutation in plasma to identify suitable patients. * To explore potential pharmacodynamic (PD) markers of KRASG12C and EGFR inhibition in tumor tissue and/or blood plasma. * To explore correlations between baseline tumor biomarkers, gene alterations, and clinical activity/efficacy. * To define mechanisms of acquired resistance to EGFR and KRASG12C inhibition and evaluate novel strategies to overcome such resistance. * To assess pharmacokinetics of MRTX849 and irinotecan and key metabolites.