BRAF V600 mutations serve as oncogenic drivers in non-small cell lung cancer (NSCLC). The BRAF V600E mutation accounts for 1% to 2% of NSCLCs. The latest guidelines from ESMO endorse the use of dabrafenib in conjunction with trametinib as the preferred first-line treatment or as a subsequent therapeutic option for patients with advanced NSCLC harboring BRAF V600E mutations. Additionally, the combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib has shown clinical effectiveness in individuals with BRAF V600E-mutant NSCLC and melanoma. Based on the results from this study, the Food and Drug Administration and European Medicines Agency approved the encorafenib plus binimetinib combination for patients with BRAF V600E-mutant metastatic NSCLC (in October 2023 and August 2024, respectively).
This ongoing, open-label, single-arm phase 2 study (IFCT-1904) included patients with BRAF V600E-mutant NSCLC who received encorafenib at a dose of 450 mg once daily combined with binimetinib at 45 mg twice daily. The study was divided into 2 cohorts: cohort A, which comprised patients who had not been previously treated, and cohort B, which included those who had received prior therapies. The primary end point was the overall response rate (ORR) evaluated by investigators, while secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety evaluations.
A total of 64 patients were enrolled in cohort A from 24 centers located in France, with the enrollment period spanning from March 2021 to September 2023. The median age of the cohort was 70.7 years, and 46.9% of the participants were male. Among the patients, 17.2% had brain metastases at baseline, and 35.9% were classified as never-smokers. The study’s median follow-up duration was 18 months. The ORR, as determined by investigators, was 66.6%. The median DOR was 13 months, and the DCR was 85.2%. The median PFS was 10.91 months, while the median OS has not been reached. The most commonly reported treatment-related adverse events (TRAEs) included fatigue (42.2%), nausea (32.8%), and diarrhea (31.3%). Among the patients, 34.4% experienced at least 1 dose reduction of encorafenib, while 32.8% had a dose reduction of binimetinib, with 90% of these reductions attributed to adverse events. Furthermore, grade 3 TRAE retinal detachment was reported in 3 patients (4.7%).
In this phase 2 trial involving treatment-naïve patients with BRAF V600E-mutant advanced NSCLC, the combination of encorafenib and binimetinib exhibited significant clinical efficacy. The safety profile was found to be manageable and aligned with findings from earlier studies conducted in lung cancer and melanoma.
Source: Planchard D, Mazieres J, Mascaux C, et al. Encorafenib plus binimetinib in patients (pts) with previously untreated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC): an open-label, multicenter phase II trial (IFCT-1904 ENCO-BRAF). Barcelona, Spain, & online: presented at ESMO Congress 2024; abstract 1259MO.