avutometinib + cetuximab

Avutometinib (VS-6766) is a first-in-class, oral, small molecule dual RAF/MEK inhibitor, also referred to as a RAF/MEK clamp. It works by inhibiting MEK kinase activity and inducing dominant negative RAF/MEK complexes that prevent the re-activation of MEK by RAF. In the context of the University of Chicago's Phase 1b/2 clinical trial (NCT05200442), it is being evaluated in combination with cetuximab, a chimeric monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR). This combination therapy is specifically designed for patients with advanced KRAS-mutated metastatic colorectal cancer who have progressed on prior therapies. By inhibiting both the upstream EGFR receptor and the downstream RAF/MEK signaling nodes, the regimen aims to overcome the inherent resistance of KRAS-mutated tumors to standard EGFR inhibition, which are typically unresponsive to EGFR blockade alone.

Other names

VS-6766 + cetuximabavutometinib and cetuximab