adagrasib + BI 1701963

Adagrasib + BI 1701963 is an oral combination of two small molecule inhibitors being evaluated for the treatment of advanced solid tumors, particularly those harboring the KRAS G12C mutation. Adagrasib (MRTX849) is a covalent, irreversible inhibitor that targets KRAS G12C in its inactive state, thereby blocking KRAS-dependent signaling pathways implicated in tumor growth and survival. BI 1701963 is a selective, oral inhibitor of SOS1, a guanine nucleotide exchange factor that activates KRAS, acting as a pan-KRAS inhibitor. The combination aims to suppress oncogenic RAS-MAPK pathway signaling more effectively than either drug alone, showing enhanced anticancer effects and a delay in the emergence of acquired resistance in preclinical models[1][4][6]. The regimen is under investigation in Phase 1 clinical trials for unresectable or metastatic solid tumors, with dose escalation and expansion cohorts focused on non-small cell lung cancer (NSCLC) and colorectal cancer (CRC)[1][4][5][7].

Other names

adagrasib + BI 1701963