FDA Okays Genentech's Cotellic In Combination With Zelboraf In Advanced Melanoma

The study found that the new therapy extends lives and decreases the risk of side-effects in men and women with melanoma

Cotellic (cobimetinib) in combination with another chemotherapy, vemurafenib (Zelboraf), has been approved by the U.S. Food and Drug Administration to treat melanoma skin cancer that has spread or can’t be surgically removed, and that has a BRAF V600E or V600K mutation, the agency said Tuesday in a news release.

Like Mekinist (trametinib), Cotellic (cobimetinib) is a mitogen-activated protein kinase (MEK) inhibitor and has been approved for use alongside Genentech's BRAF inhibitor Zelboraf (vemurafenib) in patients with BRAF V600-positive advanced melanoma. An interim analysis also showed the combination of Cotellic and Zelboraf helped people live significantly longer (overall survival; OS) than Zelboraf alone (HR=0.63, 95 percent CI 0.47-0.85; p=0.0019).

Today's 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.

Cotellic was reviewed under the FDA's priority review program that provides for an expedited six-month review of drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. He added, "For patients with a BRAF mutated melanoma, the combination has higher activity to shrink their tumors, and with less side effects than the drugs on their own".

Between 60% and 80% of patients withBRAFV600E-mutant melanoma who receive single-drug treatment with the BRAF inhibitor vemurafenib experience a complete response, and a significant number acquire resistance to the drug within one year.

This mutation can be treated with vemurafenib, which was recently approved by the FDA. The objective response rate (ORR) with the combination was 69.6% compared with 50% for vemurafenib alone. The most common adverse events seen in the combination arm included diarrhea, nausea, rash, photosensitivity and laboratory test abnormalities.

"Combining two or more treatments addressing different cancer-causing targets may help to address this challenge", Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in an interview.


The scientific basis of this research builds upon prior studies at UCLA led by Dr. Roger Lo, a Jonsson Comprehensive Cancer Center member and associate professor of medicine, who had described the mechanisms of how melanoma became resistant to vemurafenib and that the addition of a drug like cobimetinib would prevent these mechanisms. J Clin Oncol. 2015;33 (suppl; abstr 9006).