avutometinib + sotorasib + defactinib

Avutometinib + sotorasib + defactinib is an investigational combination therapy being studied primarily for the treatment of KRAS G12C-mutant non-small cell lung cancer (NSCLC) and other RAS/MAPK-driven tumors. Avutometinib is an oral RAF/MEK clamp that inhibits MEK1/2 kinase activities and induces inactive complexes with ARAF, BRAF, and CRAF, resulting in maximal inhibition of the RAS/MAPK pathway. Sotorasib is a small molecule inhibitor specifically targeting KRAS G12C mutations. Defactinib is an oral selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), which are involved in cell proliferation, survival, migration, invasion, and resistance to anti-cancer agents including RAF and MEK inhibitors. The combination aims to provide a more comprehensive blockade of oncogenic signaling pathways implicated in tumor growth and drug resistance[1][3][8].

Brand names

LUMAKRAS (for sotorasib)