Adagrasib: a novel inhibitor for KRAS G12C -mutated non-small-cell lung cancer.

Adagrasib is a recently US FDA-approved novel KRAS G12C targeted therapy with clinical efficacy in patients with advanced, pretreated KRAS G12C -mutated non-small-cell lung cancer. KRYSTAL-I reported an objective response rate of 42.9% with median duration of response of 8.5 months. Treatment-related adverse events were primarily gastrointestinal and occurred in 97.4% of patients, with grade 3+ treatment-related adverse events occurring in 44.8% of patients. This review details the preclinical and clinical data for adagrasib in the treatment of non-small-cell lung cancer. We also outline practical clinical administration guidelines for this novel therapy, including management of toxicities. Finally, we discuss the implications of resistance mechanisms, summarize other KRAS G12C inhibitors currently in development and outline future directions for adagrasib-based combination therapies.