Cobimetinib Receives Priority Review for Advanced Melanoma

The FDA has granted a priority review to the MEK inhibitor cobimetinib for use in combination with the BRAF inhibitor Zelboraf to treat patients with BRAF V600–positive advanced melanoma.

The Food and Drug Administration has granted a priority review to the MEK inhibitor cobimetinib for use in combination with the BRAF inhibitor Zelboraf (vemurafenib) to treat patients with BRAF V600—positive advanced melanoma. A final approval decision will come from the FDA by August 11, 2015.

The priority review is based on data from the phase 3 coBRIM study, in which the cobimetinib/Zelboraf combination reduced the risk of disease progression by 49 percent versus Zelboraf alone. Median progression-free survival (PFS) was improved by 3.7 months with cobimetinib.

The international, double-blind, phase 3 coBRIM trial randomized 495 patients to continuous Zelboraf plus placebo or cobimetinib. Treatment was administered until progression or unacceptable toxicity.

Patients had histologically confirmed unresectable, locally advanced stage 3C or 4 melanoma with a BRAF V600 mutation as detected by the Cobas 4800 BRAF V600 Mutation Test. The median patient age in both arms was about 55 years, and all patients had an ECOG performance status of 0 or 1.

PFS was the primary endpoint, with secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response and safety.

Median PFS was significantly improved in the cobimetinib arm, at 9.9 months compared with 6.2 months in patients receiving Zelboraf alone. ORR was 68 percent in the combination arm versus 45 percent with single-agent Zelboraf.

The most frequently reported adverse events of all grades reported in the cobimetinib arm versus the control arm included diarrhea, nausea, photosensitivity, among others. Hair loss and joint pain were less frequent with cobimetinib.

Treatment-related discontinuation rates in the combination and control groups were similar at 13 percent and 12 percent, respectively. There were six deaths related to side effects in the cobimetinib arm and three in the control arm.

Single-agent Zelboraf was approved by the FDA in 2011 for the treatment of patients with advanced melanoma who have a BRAF V600E mutation.

[Read "Zelboraf gets early FDA approval" from Aug. 17, 2011]

CURE will feature advances in melanoma in the Winter 2015 issue.