onartuzumab + vemurafenib + cobimetinib

This is a **triple combination therapy** consisting of *onartuzumab* (a monoclonal antibody targeting the MET receptor), *vemurafenib* (a small molecule BRAF inhibitor), and *cobimetinib* (a small molecule MEK inhibitor). Onartuzumab binds and inhibits MET signaling, which is implicated in tumor growth and resistance mechanisms. Vemurafenib targets mutant BRAF V600 proteins in the MAPK pathway, while cobimetinib inhibits MEK1/2, downstream effectors in the same pathway. Vemurafenib + cobimetinib is an FDA-approved combination for BRAF V600-mutated metastatic melanoma, shown to improve progression-free and overall survival compared to monotherapy[1][2][3][4][5]. Onartuzumab has primarily been investigated in combination with other targeted therapies in solid tumors, with the rationale that MET inhibition may overcome resistance to BRAF/MEK inhibitors. However, there is no evidence from available sources of clinical use or regulatory approval for this specific triple combination (onartuzumab + vemurafenib + cobimetinib); the standard investigated and approved combination is vemurafenib + cobimetinib.