The FDA has accepted and granted priority review for a New Drug Application (NDA) for cobimetinib in combination with vemurafenib (Zelboraf, Genentech) 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 inside cells that 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.
The NDA was based on results from the coBRIM study, an international, randomized, double-blind, placebo-controlled, Phase III study evaluating the safety and efficacy of 60 mg once daily of cobimetinib in combination with 960 mg twice daily of vemurafenib compared to 960 mg twice daily of vemurafenib alone. Results demonstrated that people who received the MEK inhibitor cobimetinib plus vemurafenib lived significantly longer without their disease worsening or death (progression-free survival; PFS) compared to vemurafenib alone. Cobimetinib plus vemurafenib reduced the risk of disease worsening or death by half in people who received the combination, with a median PFS of 9.9 months 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.
