FDA approves Cotellic (cobimetinib) + Zelboraf (vemurafenib) to treat BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma- Genentech + Roche

Genentech, a member of the Roche Group, announced that the FDA approved Cotellic (cobimetinib) for the treatment of people with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in combination with Zelboraf (vemurafenib). Cotellic and Zelboraf are not used to treat melanoma with a normal BRAF gene. Cotellic is Genentech’s seventh new medicine approved by the FDA in the past five years.

This FDA approval is based on results from the Phase III coBRIM study, which showed Cotellic plus Zelboraf reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination (HR=0.56, 95 percent CI 0.45-0.70; p<0.001), with a median PFS of 12.3 months for Cotellic plus Zelboraf compared to 7.2 months with Zelboraf alone. An interim analysis also showed the combination of Cotellic and Zelboraf helped people live significantly longer (overall survival) than Zelboraf alone (HR=0.63, 95 percent CI 0.47-0.85; p=0.0019). The objective response rate (tumor shrinkage) was higher with Cotellic plus Zelboraf compared to Zelboraf alone (70 vs. 50 percent; p<0.001), as was the complete response rate (complete tumor shrinkage, 16 vs. 10 percent).

Comment: Combining the two mechanisms of action (MEK and BRAF inhibition) is expected to change the standard of care in this indication, by providing more complete blockade of the MAP kinase pathway to delay the emergence of resistance.

Comment: In September, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) issued a positive opinion for Roche’s marketing authorization application for Cotellic in the European Union. A decision from the European Commission is expected before the end of 2015.