The phase 3 COLUMBUS trial, designed to evaluate binimetinib plus encorafenib for the treatment of BRAF–mutant melanoma, met its primary endpoint of improving PFS over vemurafenib, according to the drug’s manufacturer.
These results also were presented at the Society for Melanoma Research Congress in Boston.
In part 1 of the trial, researchers randomly assigned 577 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutations to receive 45 mg binimetinib (MEK162, Array BioPharma) plus 450 mg of encorafenib (LGX818, Array BioPharma), 300 mg encorafenib monotherapy or 960 mg vemurafenib (Zelboraf, Genentech) monotherapy.
Patients treated with the combination therapy compared with vemurafenib alone demonstrated superior PFS (14.9 vs. 7.3 months; HR = 0.54; 95% CI, 0.41-0.71).
In addition, patients in the combination therapy arm demonstrated superior ORR (63% vs. 40%), a longer duration of response (51 weeks vs. 31 weeks) and received a higher median dose intensity (100% vs. 99.6%) compared with the vemurafenib arm.
Grade 3 or grade 4 adverse events included increased gamma-glutamyl transferase and blood creatine phosphokinase, as well as hypertension. Adverse events of special interest consisted of rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%).
“The robust PFS benefit and tolerability observed with binimetinib plus encorafenib in COLUMBUS suggest the combination represents a potential important addition to the MEK/BRAF treatment landscape for patients with BRAF–mutant melanoma,” Victor Sandor, chief medical officer at Array BioPharma, said in a press release. “We are preparing these data for regulatory submission in 2017.”
Results from part 2 of the trial — designed to provide additional data from 344 patients to evaluate the addition of binimetinib to encorafenib — is anticipated for mid-2017, the release said. – by Kristie L. Kahl