Melanoma patients with BRAF mutations may benefit more from the combination of encorafenib and binimetinib, two investigational medicines, than from Zelboraf (vemurafenib) monotherapy, according to data from the first part of a Phase 3 study. The study has reached its primary endpoint, demonstrating higher progression-free survival (PFS) rates in the combination therapy group.
“The COLUMBUS Part 1 trial results demonstrate a robust PFS benefit associated with the combination of binimetinib plus encorafenib versus vemurafenib in patients with BRAF-mutant melanoma,” Ron Squarer, CEO of Array BioPharma, said in a press release. “We look forward to working with global regulatory authorities as they evaluate our planned submission.”
The COLUMBUS Phase 3 trial (NCT01909453) is an international randomized study, evaluating the effectiveness and safety of encorafenib and binimetinib combination versus Zelboraf or encorafenib alone in patients with locally advanced, unresectable, or metastatic melanoma with the BRAF V600 mutation.
Zelboraf and encorafenib are BRAF inhibitors, and binimetinib is a MEK inhibitor. Only Zelboraf has been approved by the Food and Drug Administration.
The trial was divided into two distinct parts.
In the first part, 577 patients were randomized to receive either 450 mg encorafenib plus 45 mg binimetinib, 960 mg Zelboraf alone, or 300 mg encorafenib alone. The study’s primary endpoint was a PFS benefit of the combination therapy versus Zelboraf. Secondary endpoints included the comparison of overall survival between the combination therapy and Zelboraf and comparison of PFS in the combination group and encorafenib group. Objective response rates, disease control rates, and safety endpoint were also assessed in this part of the study.
Part 2 includes 344 patients randomized to receive either 300 mg encorafenib plus 45 mg binimetinib, or 300 mg encorafenib alone. This part was designed to provide additional data regarding the contribution of binimetinib to the combination therapy effects.
Preliminary data from the first part shows a median PFS of 14.9 months for patients treated with encorafenib plus binimetinib combination compared to 7.3 months in those treated with Zelboraf alone. The researchers also report adverse events that are consistent with a previous combination of these therapies in other clinical trials for melanoma patients.
“The preliminary results from Part 1 of COLUMBUS suggest that the combination of encorafenib plus binimetinib represents a potentially unique therapy for the BRAF-mutant melanoma population,” said Dr. 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 addition to the robust activity observed in Part 1, the combination appeared to be generally well-tolerated.”
Results from Part 1 suggested improved PFS in the combination group versus the encorafenib monotherapy group (14.9 vs 9.6 months), but the results did not reach statistical significance.
Array Biopharma will soon present additional results from COLUMBUS Part 1 at an upcoming medical meeting, and expects to reveal data from Part 2 in mid 2017. This data will also be submitted to global health authorities to obtain approval for these product candidates.
“We are very pleased with the COLUMBUS Part 1 results and look forward to the possibility that, if approved, the combination of encorafenib plus binimetinib could offer a new treatment option for patients suffering from this devastating disease,” said Frédéric Duchesne, CEO of the pharmaceutical division at Pierre Fabre.
