Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non-small-cell lung cancer

Riely, G.J.; Smit, E.F.; Ahn, M.J.; Felip, E.; Ramalingam, S.S.; Tsao, A.; ... ; Johnson, B.E. (2023)

Article / Letter to editor

PURPOSE The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAF(V600E/K)-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC).METHODS In this ongoing, open-label, single-arm, phase II study, patients with BRAF(V600E)-mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.RESULTS At data cutoff, 98 patients (59 treatment-naive and 39 previously treated) with BRAF(V600E)-mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naive and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naive and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naive and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard ().CONCLUSION For patients with treatment-naive and previously treated BRAF(V600E)-mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.

• All authors: Riely, G.J.; Smit, E.F.; Ahn, M.J.; Felip, E.; Ramalingam, S.S.; Tsao, A.; Johnson, M.; Gelsomino, F.; Esper, R.; Nadal, E.; Offin, M.; Provencio, M.; Clarke, J.; Hussain, M.; Otterson, G.A.; Dagogo-Jack, I.; Goldman, J.W.; Morgensztern, D.; Alcasid, A.; Usari, T.; Wissel, P.; Wilner, K.; Pathan, N.; Tonkovyd, S.; Johnson, B.E.
• Date: 2023-07-20
• Journal: Journal of Clinical Oncology
• Volume: 41
• Issue: 21
• Pages: 3700 - 3711
• DOI: doi:10.1200/JCO.23.00774
• Link: https://ascopubs.org/doi/10.1200/JCO.23.00774