Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer

Author(s): Gregory J. Riely, MD, PhD1; Egbert F. Smit, MD, PhD2; Myung-Ju Ahn, MD, PhD3; Enriqueta Felip, MD, PhD4; Suresh S. Ramalingam, MD5; Anne Tsao, MD6; Melissa Johnson, MD7; Francesco Gelsomino, MD8; Raymond Esper, MD, PhD9; Ernest Nadal, MD, PhD10; Michael Offin, MD1; Mariano Provencio, MD, PhD11; Jeffrey Clarke, MD12; Maen Hussain, MD9; Gregory A. Otterson, MD13; Ibiayi Dagogo-Jack, MD14; Jonathan W. Goldman, MD15; Daniel Morgensztern, MD16; Ann Alcasid, BA17; Tiziana Usari, BSc18; Paul Wissel, MD19; Keith Wilner, PhD20; Nuzhat Pathan, PhD20; Svitlana Tonkovyd, MD21; and Bruce E. Johnson, MD22
Source: DOI: 10.1200/JCO.23.00774 Journal of Clinical Oncology 41, no. 21 (July 20, 2023) 3700-3711.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Targeted therapy in NSCLC, FCS was part of this trial.


The 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).


In 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.


At 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 (


For 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.

Author Affiliations

1Memorial Sloan Kettering Cancer Center, New York, NY;2Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, the Netherlands;3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;4Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain;5Winship Cancer Institute of Emory University, Atlanta, GA;6MD Anderson Cancer Center, Houston, TX;7Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN;8Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;9Florida Cancer Specialists, Fort Myers, FL;10Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain;11Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain;12Duke Cancer Center, Durham, NC;13Ohio State University Comprehensive Cancer Center, Columbus, OH;14Massachusetts General Hospital, Boston, MA;15David Geffen School of Medicine at UCLA, Los Angeles, CA;16Washington University School of Medicine, St Louis, MO;17Pfizer, Collegeville, PA;18Pfizer, Milan, Italy;19Pfizer, New York, NY;20Pfizer, La Jolla, CA;21Pfizer, Warsaw, Poland;22Dana-Farber Cancer Institute, Boston, MA

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