Encorafenib Plus Binimetinib for BRAF V600E-Mutant Advanced Non-Small Cell Lung Cancer in the First-Line Setting

According to primary results from the phase 2 IFC-1904 ENCO-BRAF trial, encorafenib plus binimetinib showed encouraging clinical activity among treatment-naïve patients with BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC).

These results were first presented by David Planchard, MD, Gustave Roussy, Villejui, France, at the 2024 European Society for Medical Oncology (ESMO) Congress.

The preferred first-line option for patients with BRAF V600E NSCLC, according to current ESMO guidelines, is dabrafenib plus trametinib. Previously, the combination of the BRAF inhibitor encorafenib and MEK inhibitor binimetinib has shown clinical efficacy for patients with BRAF V600E NSCLC and melanoma.

Cohort A of this ongoing, open-label, single-arm trial enrolled 64 patients who had not yet received treatment with BRAF V600E-mutant NSCLC. Cohort B, not presented in this report, enrolled patients who had received previous treatment. Patients in this trial received 450 mg encorafenib daily plus 45 mg binimetinib twice daily. The primary end point was overall response rate (ORR), as assessed by investigators. Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

The median follow-up duration was 18 months. The median duration of treatment was 8.8 month with encorafenib and 8.9 months with binimetinib. The investigator-assessed ORR was 66.7%, with median DOR at 13 months. The DCR was 85.7%. The median PFS was 11.1 months, and the median OS was not reached. The most common treatment-related adverse events were fatigue (42.4%), nausea (32.8%), and diarrhea (31.3%). There were 3 patients (4.7%) who experienced a grade 3 treatment-related retinal detachment. There were 15.8% of patients who permanently discontinued the regimen due to a treatment-related adverse event.

Dr Blanchard et al concluded, “encorafenib plus binimetinib demonstrated robust clinical activity” while “the safety profile was manageable and consistent with previous studies in lung cancer and melanoma.”

Source:

Planchard D, Marzieres 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 (IFC-1904 ENCO-BRAF). Presented at the 2024 ESMO Congress. September 13-17, 2024; Barcelona, Spain. Abstract: 1259MO.