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Positive overall survival results from coBRIM, the phase 3 pivotal trial evaluating Cobimetinib, a specific MEK inhibitor, in combination with Vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma carrying a BRAF V600 mutation, were presented.
coBRIM met its secondary endpoint of demonstrating a statistically significant and clinically meaningful increase in overall survival for patients receiving the combination of Cobimetinib and Vemurafenib, as compared to Vemurafenib monotherapy. Ongoing study monitoring did not identify any new safety signals.

The coBRIM trial is 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.
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 Vemurafenib every day on a 28-day cycle plus either Cobimetinib or placebo for 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, overall response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures.

Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway ( the RAS-RAF-MEK-ERK pathway ) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components ( BRAF ) causes abnormal activation in about 50% of tumors. About 50% of patients with BRAF mutation positive melanoma experience a tumor response when treated with a BRAF inhibitor, however development of resistance and subsequent tumor progression limits treatment benefit.
Clinical and preclinical analyses indicated that reactivation of the MEK-ERK pathway may underlie development of resistance to BRAF inhibitors in many progressing tumors, and that co-treatment with a BRAF and MEK inhibitor delays the emergence of resistance in the preclinical setting, providing the rationale for testing the combination of Vemurafenib and Cobimetinib in clinical trials.

Source: Exelixis, 2015

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