FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation
Regulatory approval: On Oct 11, 2023, the FDA approved encorafenib plus binimetinib for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring a BRAF V600E mutation detected by an FDA-approved test. Approval was supported by the single-arm PHAROS study (n=98). In treatment-naïve patients, ORR was 75% and median DoR was not estimable; in previously treated patients, ORR was 46% with median DoR 16.7 months.
FDA approval (Oct 11, 2023)
The US Food and Drug Administration (FDA) approved encorafenib (Braftovi) in combination with binimetinib (Mektovi) for adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
The FDA also approved FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for encorafenib plus binimetinib. If no mutation is detected in a plasma specimen, tumor tissue should be tested.
Supporting evidence
Efficacy was evaluated in PHAROS (NCT03915951), an open-label, multicenter, single-arm study enrolling 98 patients with metastatic BRAF V600E–mutant NSCLC; prior BRAF or MEK inhibitors were not allowed. Patients received encorafenib plus binimetinib until disease progression or unacceptable toxicity.
Major endpoints were objective response rate (ORR) (RECIST v1.1) and duration of response (DoR) assessed by an independent review committee:
- Treatment-naïve (n=59): ORR 75% (95% CI 62–85); median DoR not estimable (NE) (95% CI 23.1–NE).
- Previously treated (n=39): ORR 46% (95% CI 30–63); median DoR 16.7 months (95% CI 7.4–NE).
Safety and dosing
Most common adverse reactions (≥25%) were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough. Recommended doses in this setting: encorafenib 450 mg PO once daily plus binimetinib 45 mg PO twice daily.