On October 11, 2023, the Food and Drug Administration approved encorafenib (Braftovi, Array BioPharma Inc., a wholly owned subsidiary of Pfizer) with binimetinib (Mektovi, Array BioPharma Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
FDA also approved the FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for encorafenib with binimetinib. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.
Efficacy was evaluated in 98 patients with metastatic NSCLC with BRAF V600E mutation enrolled in PHAROS (NCT03915951), an open-label, multicenter, single-arm study. Prior BRAF or MEK inhibitors was not allowed. Patients received encorafenib and binimetinib until disease progression or unacceptable toxicity.
The major efficacy outcome measures were objective response rate (ORR) per RECIST v1.1 and duration of response (DoR), as assessed by an independent review committee. Among 59 treatment-naïve patients, ORR was 75% (95% CI: 62, 85); median DoR was not estimable (NE) (95% CI: 23.1, NE). Among 39 previously treated patients, ORR was 46% (95% CI: 30, 63) with a median DoR of 16.7 months (95% CI: 7.4, NE).
The most common adverse reactions (≥25%) were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.
The recommended doses for BRAF V600E mutation-positive NSCLC are encorafenib 450 mg orally once daily and binimetinib 45 mg orally twice daily.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.