Adagrasib with or without cetuximab for metastatic colorectal cancer with mutated KRAS G12C

Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy. A multicenter phase 1-2 trial in the United States evaluated adagrasib with or without cetuximab for heavily pretreated metastatic colorectal cancer with KRAS G12C mutation. Adagrasib had antitumor activity, both as oral monotherapy and in combination with cetuximab. The median response duration was longer than 6 months in the combination-therapy group. Reversible adverse events were common in both groups.