Adagrasib

Adagrasib (MRTX849) is an oral, small-molecule KRAS inhibitor developed by Mirati Therapeutics. KRAS mutations are highly common in cancer and account for approximately 85% of all RAS family mutations. However, the development of KRAS inhibitors has been challenging due to their high affinity for guanosine triphosphate (GTP) and guanosine diphosphate (GDP), as well as the lack of a clear binding pocket. Adagrasib targets KRAS, one of the most common KRAS mutations, at the cysteine 12 residue and inhibits KRAS-dependent signalling. In a phase I/IB clinical study that included patients with KRAS-mutated advanced solid tumors (NCT03785249), adagrasib exhibited anti-tumor activity. The phase II of the same study showed that in patients with KRAS-mutated non-small-cell lung cancer (NSCLC), adagrasib was efficient without new safety signals. In February 2022, the FDA accepted a new drug application (NDA) for adagrasib for the treatment of patients with previously treated KRAS–positive NSCLC. In December 2022, the FDA granted accelerated approval to adagrasib for the treatment of KRAS-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. Adagrasib joins sotorasib as another KRAS inhibitor approved by the FDA.