LY3214996 + encorafenib + cetuximab

LY3214996 + encorafenib + cetuximab is an investigational combination therapy for advanced/metastatic cancer, especially in tumors driven by dysregulation of the RAS/RAF/MEK/ERK MAPK pathway such as BRAF or KRAS mutant cancers. LY3214996 is a potent, selective, ATP-competitive inhibitor of extracellular signal-regulated kinases ERK1/2, key downstream effectors in the MAPK pathway, developed to overcome resistance to upstream MAPK inhibitors. Encorafenib is a small molecule inhibitor targeting BRAF V600E kinase, while cetuximab is a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). The triple combination seeks to simultaneously target multiple nodes of oncogenic signaling in MAPK pathway-activated cancers, aiming to provide superior tumor growth inhibition and address acquired resistance to BRAF and EGFR inhibitors. This combination is under clinical investigation and not yet approved for standard use.