The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for Genentech’s New Drug Application (NDA) for cobimetinib in combination with vemurafenib (Zelboraf) for the treatment of people with BRAF V600 mutation–positive advanced melanoma. The FDA will make a decision on approval by August 11, 2015.
Cobimetinib is designed to selectively block the activity of MEK, one of a series of proteins make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while vemurafenib binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumors to grow.
Phase III coBRIM Study
The NDA is based on results of the phase III coBRIM study, which evaluated the safety and efficacy of cobimetinib plus vemurafenib vs vemurafenib alone in 495 patients with BRAF V600 mutation–positive unresectable locally advanced or metastatic melanoma who had not previously been treated for advanced disease. Patients were randomly assigned to receive vemurafenib every day on a 28-day cycle plus either cobimetinib or placebo on days 1 to 21. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed progression-free survival.
Cobimetinib plus vemurafenib reduced the risk of disease worsening or death by half in people who received the combination (hazard ratio = 0.51, 95% confidence interval = 0.39–0.68, P < .0001). The median progression-free survival was 9.9 months for cobimetinib plus vemurafenib compared to 6.2 months with vemurafenib alone.
The safety profile was consistent with a previous study of the combination. The most common grade 3 or higher adverse events in the combination arm included liver lab value abnormalities, elevated creatine phosphokinase, and diarrhea. The most common adverse events seen in the combination arm included diarrhea, nausea, rash, photosensitivity, and lab value abnormalities. ■