Updated Efficacy and Safety From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic NSCLC—A Brief Report
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: INTRODUCTION: The PHAROS primary analysis revealed robust antitumor activity and acceptable safety with encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC). We report results after 18 months of additional follow-up. METHODS: In this ongoing open-label, single-arm, phase 2 study, patients with BRAF V600E-mutant mNSCLC (59 treatment-naive and 39 previously treated) received encorafenib 450 mg once daily and binimetinib 45 mg twice daily. Primary end point was objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: At this data cutoff, median treatment duration with encorafenib plus binimetinib was 16.3 months in treatment-naive and 5.5 months in previously treated patients; minimum follow-up was approximately 32 and 22 months, respectively. In treatment-naive patients, the ORR was 75%, median DOR was 40.0 months, median PFS was 30.2 months, median OS was not estimable (95% confidence interval: 31.3-not estimable), and the 3-year OS probability was 53%. In previously treated patients, the ORR was 46%, median DOR was 16.7 months, median PFS was 9.3 months, median OS was 22.7 months, and the 3-year OS probability was 29%. Overall, the most frequent treatment-related adverse events were nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%). Treatment-related adverse events led to dose reductions and permanent treatment discontinuations in 25 (26%) and 16 (16%) patients, respectively. CONCLUSIONS: With longer follow-up, encorafenib plus binimetinib showed durable and clinically meaningful antitumor activity, especially in treatment-naive patients, with a manageable safety profile in patients with BRAF V600E-mutant mNSCLC. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT03915951.
Source: Journal of Thoracic Oncology
Authors: Gregory J. Riely, Myung-Ju Ahn, Jeffrey M. Clarke, Ibiayi Dagogo-Jack, Raymond Esper, Enriqueta Felip, Francesco Gelsomino, Jonathan W. Goldman, Maen Hussein, Melissa Johnson, Kristen A. Marrone, Daniel Morgensztern, Ernest Nadal, Marcelo V. Negrao, Michael Offin, Mariano Provencio, Suresh S. Ramalingam, Logan Roof, Rachel E. Sanborn, Egbert F. Smit, Anne Tsao, Tiziana Usari, Ann Alcasid, Keith Wilner, Svitlana Tonkovyd, Xiaosong Zhang, Bruce E. Johnson
Institutions: Memorial Sloan Kettering Cancer Center, Samsung Medical Center, Sungkyunkwan University, Duke University, Duke Medical Center, Duke Cancer Institute, Massachusetts General Hospital, Vall d'Hebron Institute of Oncology, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of California, Los Angeles, Tennessee Oncology, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Washington University in St. Louis, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, The University of Texas MD Anderson Cancer Center, Hospital Universitario Puerta de Hierro Majadahonda, Winship Cancer Institute, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Providence Portland Medical Center, Leiden University Medical Center, Pfizer (Italy), Pfizer (United States), Dana-Farber Cancer Institute
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,100
Funders: U.S. Department of Defense, Mesothelioma Applied Research Foundation, LUNGevity Foundation, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, International Association for the Study of Lung Cancer, Ariad Pharmaceuticals, Spectrum Pharmaceuticals, Celgene, F. Hoffmann-La Roche, Memorial Sloan-Kettering Cancer Center, Karyopharm Therapeutics, Array BioPharma, Helsinn, Regeneron Pharmaceuticals, Exelixis, Jazz Pharmaceuticals, Novocure, Les Laboratories Pierre Fabre, Tizona Therapeutics, Mirati Therapeutics, BeiGene, Incyte, Calithera Biosciences, Syndax Pharmaceuticals, Ribon Therapeutics, Apollomics, Yuhan, Revolution Medicines, Relay Therapeutics, Puma Biotechnology, Moderna, EpicentRx, G1 Therapeutics, EQRx, Seagen, Natera, Y-mAbs Therapeutics, Coherus Biosciences, Ono Pharmaceutical, Ipsen, Grifols, Aptitude Health, Genentech, EMD Serono, Foundation Medicine, National Cancer Institute, Daiichi Sankyo Europe
OpenAlex ID: W4411023368