Array BioPharma and Pierre Fabre will present data from the COLUMBUS Phase 3 clinical trial showing that melanoma patients with BRAF mutations may benefit more from the combination of encorafenib and binimetinib, two investigational medicines, than from Zelboraf (vemurafenib) alone.
In the U.S., melanoma is the fifth most common cancer among men and the seventh among women, with more than 76,000 new cases expected to be diagnosed in 2016 alone, according to the American Cancer Society.
Studies have shown that nearly half of patients with metastatic melanoma have activating BRAF mutations, which has led to the development of new therapies that target the RAS/RAF/MEK/ERK signaling pathway.
Zelboraf and encorafenib are BRAF inhibitors, and binimetinib is a MEK inhibitor. Only Zelboraf has been approved by the U.S. Food and Drug Administration (FDA).
The randomized COLUMBUS Phase 3 trial (NCT01909453) is a multicenter study assessing the safety and effectiveness of encorafenib (450 mg) and binimetinib (45 g) combination versus Zelboraf (960 mg) alone or encorafenib (300 mg) alone in 577 patients with locally advanced, unresectable or metastatic melanoma with the BRAF V600 mutation.
As reported in September, the study met its primary endpoint of progression-free survival (PFS) in patients treated with the combination therapy (14.9 months) versus those treated with Zelboraf (7.3 months).
The results also showed that the study did not meet the secondary endpoint of higher PFS in the combination group compared to the encorafenib group. Patients treated with the combination therapy showed a median PFS of 14.9 months, and patients treated with encorafenib had a PFS 9.6 months, but the results did not reach statistical significance.
The combo treatment was generally well-tolerated. Treatment-related adverse events were consistent with those observed in previous trials assessing the combination of encorafenib with binimetinib in BRAF-mutant melanoma patients.
These results will be presented by Keith T. Flaherty, MD, director of the Termeer Center for Targeted Therapy at Massachusetts General Hospital and professor of medicine at Harvard Medical School in Boston.
Flaherty’s oral session is titled “Results of COLUMBUS Part 1: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) Versus Vemurafeib (VEM) or ENCO in BRAF-Mutant Melanoma” (Abstract 2617508).
Two other presentations will feature data from the NEMO Phase 3 study that assessed binimetinib in patients with NRAS–mutant melanoma.
Array has already submitted a New Drug Application (NDA) to the FDA for binimetib in patients with NRAS-mutant melanoma. The FDA’s action date is June 30, 2017, under the Prescription Drug User Fee Act. The company expects to submit an NDA in 2017 for the combination of binimetib and encorafenib for the treatment of melanoma patients with BRAF mutations.