Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients with BRAF V600-Mutant Metastatic Non-Small-Cell Lung Cancer

Gregory J. Riely, Egbert F. Smit, Myung Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana UsariPaul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


PURPOSEThe combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC).METHODSIn this ongoing, open-label, single-arm, phase II study, patients with BRAFV600E-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.RESULTSAt data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with BRAFV600E-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-naïve 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-naïve and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naïve 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 ( patients with treatment-naïve and previously treated BRAFV600E-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.

Original languageEnglish
Pages (from-to)3700-3711
Number of pages12
JournalJournal of Clinical Oncology
Issue number21
StatePublished - Jul 20 2023


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