avutometinib + defactinib + nivolumab

This combination therapy consists of avutometinib (VS-6766), defactinib (VS-6063), and nivolumab. Avutometinib is a novel small molecule RAF/MEK clamp that inhibits the MAPK signaling pathway by inducing the formation of dominant negative RAF-MEK complexes, thereby preventing the phosphorylation of MEK by ARAF, BRAF, and CRAF. Defactinib is a small molecule inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2). Nivolumab is a monoclonal antibody that acts as a checkpoint inhibitor by blocking the PD-1 receptor on T-cells. The triplet combination is currently being evaluated in a Phase 2 clinical trial led by Emory University for the treatment of patients with advanced lung adenocarcinoma harboring LKB1 (STK11) mutations who have previously progressed on anti-PD-1 therapy. The regimen aims to overcome immunotherapy resistance by simultaneously targeting the MAPK and FAK pathways alongside PD-1 blockade.

Brand names

OpdivoAVMAPKIFAKZYNJA

Other names

VS-6766 + VS-6063 + nivolumab