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. A BRAF V600E mutation occurs in 1% to 2% of patients with NSCLC.
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 V600K mutation, as detected by an FDA-approved test. Encorafenib plus cetuximab 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. “BRAF V600E mutations identify a unique subtype of metastatic non–small cell lung cancer that presents an actionable biomarker that precision medicines like Braftovi + Mektovi combination therapy can help address,” said Gregory Riely, MD, PhD, Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center, in a press release.
This current approval was based on data from the phase 2 PHAROS clinical trial (NCT03915951), an ongoing open-label, multicenter, single-arm study that evaluated the efficacy of these 2 kinase inhibitors, encorafenib and binimetinib, in 98 patients with metastatic NSCLC and documented BRAF V600E mutations. The 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 adverse events.
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% confidence interval [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 PHAROS trial demonstrated that patients [with BRAF V600E-mutation–positive NSCLC] could benefit from Braftovi + Mektovi targeted therapy regardless of their prior treatment history. Given the specific efficacy and safety profile, patients and providers now have another option to help personalize treatment plans based on individual risk factors and preferences,” Dr Riely stated in a press release.
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.