The European Commission has approved Cotellic ( Cobimetinib ) for use in combination with Zelboraf ( Vemurafenib ) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
The EU approval is based on data that showed Cotellic plus Zelboraf helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live for more than a year without their disease worsening.
The EU approval is based primarily on results of the phase III coBRIM study, which showed that people with previously untreated BRAF V600 mutation-positive advanced melanoma who were being treated with the MEK inhibitor Cotellic in combination with Zelboraf lived a median of one year ( 12.3 months ) without their disease worsening or death ( progression-free survival; PFS ) compared to 7.2 months with Zelboraf alone ( hazard ratio, HR=0.58; 95% confidence interval CI; 0.46-0.72 ).
The objective response rate ( ORR ) with the combination was 70% ( 16% complete response [ CR ], 54% partial response [ PR ] ) compared to 50% ( 11% CR, 40% PR ) in the Zelboraf arm.
The safety profile of Cotellic plus Zelboraf was consistent with safety data previously reported. The most common adverse events in the combination arm were diarrhea, rash, nausea, fever, sun sensitivity, liver lab abnormalities, elevated creatine phosphokinase ( CPK, an enzyme released by muscles ) and vomiting.
Additional data were presented on November 21, 2015 at the Society for Melanoma Research Congress demonstrating that the combination of Cotellic plus Zelboraf met its secondary endpoint of improving overall survival compared to Zelboraf alone.
These data will be submitted to the European Medicines Agency for consideration and inclusion in the label.
Cotellic in combination with Zelboraf is now approved in the EU and Switzerland for the treatment of people with BRAF V600 mutation-positive advanced melanoma.
In the US, the combination is approved for the treatment of people with BRAF V600E or V600K mutation-positive advanced melanoma.
CoBRIM is an international, randomised, double-blind, placebo-controlled phase III study evaluating the safety and efficacy of 60 mg once daily of Cobimetinib plus 960 mg twice daily of Vemurafenib compared to 960 mg twice daily of Vemurafenib 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 randomised to receive Vemurafenib 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 progression-free survival is the primary endpoint. Secondary endpoints include progression-free survival by independent review Committee, objective response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures. ( Xagena )
Source: Roche, 2015