This study demonstrated that MRTX1133 inhibited both the inactive and active state of KRASG12D and showed potent antitumor activity in several preclinical models of pancreatic and colorectal cancer, especially when combined with cetuximab, a monoclonal antibody against the EGFR, or BYL‐719, a potent PI3Kα inhibitor. Here, EGFR is linked to colorectal cancer.