Braftovi Plus Mektovi Now FDA Approved for Treatment of Metastatic NSCLC With BRAF Mutation

On October 11, 2023, the FDA approved a new indication for encorafenib (Braftovi; Array BioPharma) combined with binimetinib (Mektovi; Array BioPharma) for adults with metastatic non–small cell lung cancer (NSCLC) and a BRAF^V600E mutation, as detected by an FDA-approved test.

The FDA also approved 2 companion diagnostic tests, FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma), for encorafenib plus binimetinib. Tumor tissue should be tested if the BRAF^V600E mutation is not detected in plasma.

The FDA granted this application an orphan drug designation.

Encorafenib plus binimetinib was previously approved for the treatment of patients with unresectable or metastatic melanoma and a BRAF^V600E or BRAF^V600K mutation, as detected by an FDA-approved test. Encorafenib plus cetuximab (Erbitux; Eli Lilly and Company) was previously approved for the treatment of metastatic colorectal cancer in adults who have a BRAF^V600E mutation, as detected by an FDA-approved test, and have received previous therapy.

This approval was based on data from the phase 2 PHAROS study, an ongoing open-label, multicenter, single-arm clinical trial evaluating the efficacy of encorafenib and binimetinib in 98 patients with metastatic NSCLC and documented BRAF^V600E mutations. Patients were treatment naïve or had disease progression after previous therapy that did not include BRAF or MEK inhibitors. In this trial, treatment with encorafenib and binimetinib continued until disease progression or unacceptable toxicity.

The key efficacy measures included objective response rate (ORR) per RECIST v1.1 and duration of response (DOR) based on independent review committee assessment. Among the 59 treatment-naïve patients with NSCLC who received encorafenib plus binimetinib, the ORR was 75% (95% CI, 62-85). The median DOR was not estimable (95% CI, 23.1-not estimable). Among the 39 patients who received previous treatment, the ORR after receiving encorafenib plus binimetinib was 46% (95% CI, 30-63), with a median DOR of 16.7 months (95% CI, 7.4-not estimable).

The most common (≥25%) adverse events with encorafenib plus binimetinib were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.

For patients with metastatic NSCLC and BRAF^V600E mutations, the recommended dose of encorafenib is 450 mg orally once daily. The recommended dose of binimetinib is 45 mg orally twice daily.