FDA Approves Combination Therapy for Metastatic Melanoma with BRAF Mutations

This afternoon, the US Food and Drug Administration (FDA) approved Array BioPharma Inc’s encorafenib and binimetinib (BRAFTOVI and MEKTOVI) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.

In addition, the FDA also approved the THxID BRAF Kit (bioMérieux) as a companion diagnostic for these therapeutics.

The COLUMBUS trial (NCT01909453), a randomized, active-controlled, open-label, multicenter trial in 577 patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma, served as the basis for approval.

In the trial, patients were randomized (1:1:1) and administered 45 mg of binimetinib twice daily plus 450 mg of encorafenib once daily, 300 mg of encorafenib 300 mg once daily, or 960 mg of vemurafenib twice daily. Until disease progression or unacceptable toxicity, treatment continued.

Progression-free survival (PFS) using RECIST 1.1 response criteria assessed by blinded independent central review served as the major efficacy measure. For patients receiving binimetinib plus encorafenib, the median PFS was 14.9 months. For the vemurafenib monotherapy arm (hazard ratio 0.54, 95% CI: 0.41, 0.71, p<0.0001), the median PFS was 7.3 months.

By central review, respectively, overall response rates assessed were 63% and 40% while the median response duration was 16.6 months vs. 12.3 months.

Fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia included the most common (≥25%) adverse reactions in patients receiving the combination. Hemorrhage and headache were the most common adverse reactions for discontinuation of therapy; adverse reactions occurred in 5% of patients receiving the combination.

The recommended doses are 45 mg of binimetinib orally twice daily and 450 mg of encorafenib orally once daily.