First-in-human study of adagrasib for advanced KRAS G12C-mutated tumors

Mutations in KRAS occur in many tumors. KRAS^G12C mutation is seen in 3-4% of CRCs, 2% of PDACs, and lower percentage of other solid tumors. Adagrasib is a covalent inhibitor of G12C mutated KRAS. The multicenter phase 1/1b KRYSTAL-1 study evaluated adagrasib for advanced KRAS^G12C mutated tumors. Adagrasib at the R2PD (orally 600 mg twice daily) was well tolerated and exhibited antitumor activity. There were partial responses in 8 of 15 NSCLC patients (ORR 53.3%; 95% CI 26.6-78.7) with median duration of response 16.4 months, and in one of two CRC patients with median duration of response 4.2 months.