Monday September 26, 2016 0 comments
BOULDER -- Array BioPharma (Nasdaq: ARRY) and Pierre Fabre today jointly announced top-line results from Part 1 of the Phase 3 COLUMBUS (Combined LGX818 Used with MEK162 in BRAF Mutant Unresectable Skin Cancer) study evaluating LGX818 (encorafenib), a BRAF inhibitor, and MEK162 (binimetinib), a MEK inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma.
Array and Pierre Fabre said the study met its primary endpoint, significantly improving progression free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone.
"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," said Ron Squarer, Array’s CEO.
“We look forward to working with global regulatory authorities as they evaluate our planned submission."
In the analysis of the primary endpoint, the median PFS for patients treated with the combination of encorafenib plus binimetinib ("combination") was 14.9 months versus 7.3 months for patients treated with vemurafenib; HR (0.54), [95% CI 0.41-0.71], p<0.001.
The combination was generally well-tolerated and reported adverse events were overall consistent with previous combination encorafenib plus binimetinib clinical trial results in BRAF-mutant 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 Keith T. Flaherty, M.D., director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital and professor of medicine, Harvard Medical School.
"In addition to the robust activity observed in Part 1, the combination appeared to be generally well-tolerated."
Analysis of a secondary endpoint comparing the PFS of patients treated with combination to patients treated with encorafenib showed a median of 14.9 months versus 9.6 months with HR (0.75), [95% CI 0.56-1.00], p=0.051, which did not reach statistical significance.
A complete analysis of these results will be provided to global regulatory authorities as part of planned submissions. In addition, data from Part 2 of the COLUMBUS trial are anticipated in mid 2017 and will also be provided to global health authorities as part of planned regulatory submissions for approval of these product candidates.
Further results from Part 1 of the COLUMBUS trial, including objective response rates, disease control rates, safety endpoints, exploratory analyses such as a Part 1 PFS comparison of encorafenib to vemurafenib and pre-specified subgroup analyses including outcomes in patients who received prior treatment with immunotherapy will be presented at an upcoming medical meeting.
Analysis of the secondary endpoint of overall survival (OS) was not planned as part of these initial results.
"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 Frederic Duchesne, Pierre Fabre’s pharmaceutical division CEO.
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 study evaluating the efficacy and safety of the combination of encorafenib plus binimetinib to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutation.
Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the study.
Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.