This article is more than 5 years old. Information may no longer be current.

FDA accepts application for binimetinib-encorafenib combination for BRAF-mutated melanoma

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

The FDA accepted for review new drug applications that seek the use of the COMBO450 regimen to treat patients with BRAF-mutant advanced, unresectable or metastatic melanoma, according to the drugs’ manufacturer.

COMBO450 is comprised of binimetinib (MEK162, Array BioPharma), an oral small molecule MEK inhibitor, and encorafenib (LGX818, Array BioPharma), a novel oral small molecule BRAF inhibitor.

The application included data from the pivotal phase 3 COLUMBUS trial, designed to make three comparisons — COMBO450 vs. monotherapy with the BRAF inhibitor vemurafenib (Zelboraf, Genentech); COMBO450 vs. encorafenib alone; and encorafenib monotherapy vs. vemurafenib monotherapy — for patients with BRAF-mutant advanced, unresectable or metastatic melanoma. Patients assigned the COMBO450 regimen received 45 mg binimetinib twice daily and 450 mg encorafenib once daily.

COMBO450-treated patients achieved longer median PFS than those assigned vemurafenib monotherapy (14.9 months vs. 7.3 months; HR = 0.54; 95% CI, 0.41-0.71).

Patients assigned COMBO450 also achieved longer median PFS than patients who received encorafenib monotherapy (14.9 months vs. 9.6 months; HR = 0.75; 95% CI, 0.56-1).

Patients assigned encorafenib alone achieved longer median PFS than those who received vemurafenib monotherapy (9.6 months vs. 7.3 months; HR = 0.68; 95% CI, 0.52-0.9).

Adverse events among patients who received COMBO450 included rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%).

Severe adverse events included increased gamma-glutamyltransferase (9%), increased blood creatine phosphokinase (7%) and hypertension (6%).

The application also included data from the COLUMBUS part 2 trial, designed to assess the contribution of binimetinib to the combination regimen by reducing the dose of encorafenib to 300 mg in the combination arm to allow for a comparison of equal doses across arms.

Patients assigned this regimen, called COMBO300, achieved longer median PFS than those who received encorafenib alone (HR = 0.77; 95% CI, 0.61-0.97).

Tolerability in COLUMBUS part 2 appeared consistent with part 1 of the trial.

“We look forward to working with the FDA and [European Medical Agency] as they review our new drug applications for binimetinib and encorafenib,” Ron Squarer, CEO of Array BioPharma, said in a company-issued press release. “The robust PFS benefit together with the attractive tolerability profile demonstrated in COLUMBUS suggest the combination represents a potentially important addition to the MEK/BRAF treatment landscape for patients with BRAF-mutant melanoma.”

The FDA is set to make a decision by June 30, 2018.