On September 29, 2014 Exelixis reported the positive results from coBRIM, the phase 3 pivotal trial (NCT01689519) conducted by Exelixis’ collaborator Genentech, a member of the Roche Group, evaluating cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma harboring a BRAF V600 mutation (Press release Exelixis, SEP 29, 2014, View Source [SID:1234500767]).

The trial met its primary endpoint of demonstrating a statistically significant increase in investigator-determined progression-free survival (PFS). The median PFS was 9.9 months for the combination of cobimetinib and vemurafenib versus 6.2 months for vemurafenib alone (hazard ratio [HR]=0.51, 95 percent CI 0.39-0.68; p<0.0001), demonstrating the combination reduced the risk of the disease worsening by half (49 percent). The median PFS by independent review committee (IRC), a secondary endpoint, was 11.3 months for the combination arm compared to 6.0 months for the control arm (HR=0.60, 95 percent CI 0.45-0.79; p=0.0003). Objective response rate (ORR), another secondary endpoint, was 68% for the combination versus 45% for vemurafenib alone (p<0.0001). Overall survival data are not yet mature (HR=0.65, 95 percent CI 0.42-1.00; p=0.046), and at the interim analysis the p-value did not cross the prespecified boundary for significance. The safety profile of the combination was consistent with that observed in a previous study. The coBRIM data will be presented at ESMO (Free ESMO Whitepaper) 2014 today, Monday, September 29, during the Presidential Symposium by Professor Grant McArthur, Peter MacCallum Cancer Centre, Australia (Abstract #LBA5_PR, Monday, September 29, 2014, 4:00-5:20 p.m. CEST) and are also part of the official press program. Additionally, the study was published online today in the New England Journal of Medicine. Roche has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency, and Genentech plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration later this year. "Today’s presentation of data from the coBRIM trial underscore the potential for the combination of cobimetinib, an Exelixis-discovered compound, and vemurafenib to provide significant clinical benefit for patients with previously untreated BRAF V600 mutation-positive advanced melanoma," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Our partner Genentech sponsored a rigorous and well-run trial, and the results, including a significant increase in PFS and a high objective response rate, are compelling. The regulatory filing process is underway with the submission of the EU filing of the MAA. We look forward to the U.S. filing later this year and then ultimately, if approved, to supporting cobimetinib’s commercialization through our longstanding collaboration that includes a co-promotion component in the United States."