MRTX0902 + adagrasib

MRTX0902 + adagrasib is an investigational combination therapy for advanced solid tumors with mutations in the KRAS-MAPK pathway, especially those harboring the KRAS G12C mutation. MRTX0902 is a potent, selective, brain-penetrant, and orally bioavailable small molecule inhibitor of Son of Sevenless homolog 1 (SOS1), a guanine nucleotide exchange factor (GEF) that regulates KRAS activation by facilitating GDP-GTP exchange. Adagrasib (MRTX849, marketed as Krazati) is a selective small molecule covalent inhibitor of KRAS G12C, which locks KRAS G12C in its inactive, GDP-bound state. This combination is designed to provide dual vertical inhibition in the RAS/MAPK pathway: MRTX0902 prevents reactivation of KRAS by blocking SOS1, while adagrasib directly inhibits mutant KRAS G12C. The two-drug regimen aims to overcome resistance and improve antitumor effects in RAS-driven cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). The combination is in phase 1/2 clinical trials for patients with unresectable or metastatic solid tumors with relevant mutations[1][3][4][5][7][9].

Other names

no widely used alternative names for MRTX0902