Adagrasib Shows Promise in Colorectal Cancer with KRAS G12C Mutation

KRAS mutations are ubiquitous across a broad spectrum of malignancies. Adagrasib is a novel oral agent that irreversibly binds to mutant KRAS G12C protein in its inactive, GDP-bound state. Preclinical data indicate that epidermal growth factor receptor (EGFR) inhibitors may potentiate the activity of adagrasib.

Investigators report results of a phase 1–2, industry-sponsored, nonrandomized, open-label trial of adagrasib in heavily pretreated patients with metastatic colorectal cancer harboring a KRAS G12C mutation. Patients were treated either with adagrasib alone or combined with the EGFR inhibitor cetuximab. Of the 76 patients treated, most (63%) had received three or more prior regimens, most (63%) had liver metastases, and most (68%) had …