The FDA has accepted and granted Priority Review for Genentech’s, a member of the Roche Group, NDA for cobimetinib in combination with Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma. The FDA will make a decision on approval by Aug. 11.

A Priority Review designation is granted to medicines that the FDA determines have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The NDA is based on results of the coBRIM phase III study, which showed the MEK inhibitor cobimetinib plus Zelboraf reduced the risk of disease worsening or death by half in people who received the combination (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 three or higher adverse events in the combination arm included liver lab value 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 value abnormalities.

CoBRIM is an international, randomized, double-blind, placebo-controlled phase III study evaluating the safety and efficacy of 60mg once daily of cobimetinib in combination with 960mg twice daily of Zelboraf, compared to 960mg twice daily of Zelboraf alone. In the study, 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma (detected by the cobas 4800 BRAF Mutation Test) and previously untreated for advanced disease were randomized to receive Zelboraf every day on a 28-day cycle plus either cobimetinib or placebo on days 1-21.

Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent. Investigator-assessed PFS was the primary endpoint. Secondary endpoints include PFS by independent review committee, overall response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures.

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. The American Cancer Society estimates there will be more than 76,100 new cases of melanoma and approximately 9,700 melanoma deaths this year in the U.S.