An independent data monitoring committee recommended an early stop a phase III trial of Mekinist and Tafinlar in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma, following a demonstrated overall survival benefit.
The randomized, open-label study, named COMBI-v, compared the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) to vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.
Eligible patients who were randomized to the vemurafenib arm will be allowed to cross over to receive treatment with the Mekinist and Tafinlar combination.
The IDMC recommendation is based on headline data from an interim analysis that showed overall survival benefit crossing the pre-specified efficacy stopping boundary. The safety profile was consistent with previous observations of the combination. Further data analysis is underway and will be completed in the coming months, according to GlaxoSmithKline, which sponsors Mekinist and Tafinlar.
COMBI-v enrolled 704 patients in the U.S., Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia. Secondary objectives evaluated progression-free survival, overall response rate, and duration of response.
Combination use of trametinib and dabrafenib in patients with unresectable or metastatic melanoma who have BRAF V600E or K mutation is approved only in the U.S. and Australia.
Addition of Cobimetinib Boosts PFS in BRAF Mutation-Positive Patients in Phase III Trial
A phase III trial investigating a combination of the MEK inhibitor cobimetinib with the BRAF inhibitor Zelboraf increased progression-free survival, compared to Zelboraf alone, in patients with previously untreated BRAF V600 mutation-positive advanced melanoma.
Data from the study, named coBRIM, will be presented at an upcoming medical meeting, according to Genentech, which sponsors both cobimetinib and Zelboraf (vemurafenib).
“These encouraging data support the potential combined use of cobimetinib with Zelboraf to block tumor growth longer than Zelboraf alone,” said Sandra Horning, Genentech chief medical officer and head of global product development. Adverse events were consistent with those observed in a previous study of the combination.
CoBRIM is an international, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of cobimetinib in combination with Zelboraf, compared to Zelboraf alone, in 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma, previously untreated for advanced disease.
Cobimetinib is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumors to grow.
Cobimetinib was discovered by Exelixis Inc. and is being developed in collaboration with Exelixis. In addition to the combination with Zelboraf in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer and colorectal cancer.
Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal BRAF gene. Zelboraf is not used to treat melanoma with a normal BRAF gene.
