avutometinib + adagrasib

Avutometinib (VS-6766) is a small molecule RAF/MEK clamp that inhibits MEK, BRAF, and CRAF by trapping these molecules in dominant negative RAF/MEK complexes. This mechanism blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK, resulting in more complete inhibition of the RAS/MAPK pathway compared to selective MEK inhibitors. Adagrasib is a KRAS G12C inhibitor that blocks the action of abnormal KRAS G12C protein, thereby slowing or stopping cancer cell growth. The combination of avutometinib and adagrasib is being investigated for enhanced anti-tumor activity in patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC)[2][3][5][6]. Avutometinib is developed by Verastem Oncology; adagrasib's brand name is Krazati.