On 11 October 2023, the US Food and Drug Administration (FDA) 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 tumour tissue should be tested.
Full prescribing information for Braftovi and Mektovi is available here.
Efficacy was evaluated in 98 patients with metastatic NSCLC with BRAF V600E mutation enrolled in PHAROS (NCT03915951), an open-label, multicentre, 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% confidence interval [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, diarrhoea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnoea, 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.
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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.