Genentech Submits NDA to FDA for Investigational Cobimetinib Used in Combination with Zelboraf (Vemurafenib) in Advanced Melanoma

Genentech has submitted a New Drug Application (NDA) for cobimetinib to the FDA for treatment, in combination with Zelboraf (vemurafenib), for people with BRAF V600 mutation-positive advanced melanoma. The submission is based on results of the coBRIM Phase III study, which showed people who received the MEK inhibitor cobimetinib plus Zelboraf lived significantly longer without their disease worsening or death (progression-free survival; PFS) compared with Zelboraf alone.

"In the past several years we have made significant progress in treating advanced melanoma, but it remains a serious and difficult to treat cancer that affects more people each year,” said Sandra Horning, MD, chief medical officer and head of Global Product Development. “We look forward to working with the FDA as they review the NDA and hope the combination of cobimetinib and Zelboraf will soon become a new option for people with BRAF mutation-positive advanced melanoma."

In the coBRIM study, cobimetinib and Zelboraf reduced the risk of disease worsening or death by half (hazard ratio [HR]=0.51, 95% confidence interval [CI] 0.39-0.68; p<0.0001), with a median PFS of 9.9 months for cobimetinib plus Zelboraf compared to 6.2 months with Zelboraf 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 abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and diarrhea. The most common adverse events seen in the combination arm included diarrhea, nausea, rash, photosensitivity and lab abnormalities. The most common Grade 3 or higher adverse events in the combination arm included liver lab abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and diarrhea.

The results were presented at the European Society of Medical Oncology (ESMO) 2014 Congress and published in the New England Journal of Medicine. Roche has already submitted the coBRIM data to the European Medicines Agency.