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Clinical Trial
. 2025 Oct;20(10):1538-1547.
doi: 10.1016/j.jtho.2025.05.023. Epub 2025 Jun 4.

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

Gregory J Riely  1 , Myung-Ju Ahn  2 , Jeffrey M Clarke  3 , Ibiayi Dagogo-Jack  4 , Raymond Esper  5 , Enriqueta Felip  6 , Francesco Gelsomino  7 , Jonathan W Goldman  8 , Maen Hussein  5 , Melissa Johnson  9 , Kristen A Marrone  10 , Daniel Morgensztern  11 , Ernest Nadal  12 , Marcelo V Negrao  13 , Michael Offin  14 , Mariano Provencio  15 , Suresh S Ramalingam  16 , Logan Roof  17 , Rachel E Sanborn  18 , Egbert F Smit  19 , Anne Tsao  13 , Tiziana Usari  20 , Ann Alcasid  21 , Keith Wilner  22 , Svitlana Tonkovyd  23 , Xiaosong Zhang  24 , Bruce E Johnson  25
Affiliations
Clinical Trial

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

Gregory J Riely et al. J Thorac Oncol. 2025 Oct.

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.

Keywords: BRAF; Binimetinib; Encorafenib; Non–small cell lung cancer.

PubMed Disclaimer

Conflict of interest statement

Disclosure Dr. Riely has received research funding from Amgen, Novartis, Roche/Genentech, Mirati Therapeutics, Merck, Takeda, Lilly, and Pfizer; has had a consulting or advisory role with Novartis; and has received honoraria from MJH Life Sciences and DAVA Oncology. Dr. Ahn has received honoraria from AstraZeneca, MSD, Takeda, Amgen, Merck Serono, Daiichi Sankyo, Roche/Genentech, Ono Pharmaceutical, and Genexine; has had a consulting or advisory role with AstraZeneca, MSD, Takeda, Alpha Pharmaceuticals, Amgen, Merck Serono, Pfizer, Yuhan, Daiichi Sankyo, Roche/Genentech, Ono Pharmaceutical, Genexine, and BioNTech; and has received research funding from Yuhan. Dr. Clarke has had a consulting or advisory role with AstraZeneca, Bristol Myers Squibb, Coherus BioSciences, CDR-Life, Black Diamond Therapeutics, AbbVie, Amgen, Sanofi, Corbus, Janssen, Omega, G1 Therapeutics, and Bio-Thera; has received honoraria from Amgen and AstraZeneca; has received research funding from Bristol Myers Squibb, Adaptimmune, AbbVie, Moderna Therapeutics, GSK, Array BioPharma, AstraZeneca, Grid Therapeutics, Achilles Therapeutics, Genentech, CBMG, and Pfizer; and has received travel accommodations and expenses from Amgen and Bristol Myers Squibb. Dr. Dagogo-Jack has received honoraria from Foundation Medicine, Aptitude Health, Creative Educational Concepts, OncLive, American Society of Clinical Oncology, DAVA Oncology, Medscape, Total Health, Research to Practice, American Lung Association, PeerView, and Curio; has had a consulting or advisory role with Boehringer Ingelheim, AstraZeneca, Xcovery, Catalyst Pharmaceuticals, Pfizer, Syros Pharmaceuticals, BostonGene, Bayer, Genentech, Sanofi, Janssen, Bristol Myers Squibb Foundation, and Novocure; and has received research funding from Pfizer, Array BioPharma, Novartis, Genentech, Calithera Biosciences, Vivace Therapeutics, Guardant Health, BostonGene, and Tango Therapeutics. Dr. Felip has received personal honoraria for advisory board participation from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Genmab, Gilead, GSK, Janssen, Merck Serono, MSD, Novartis, Peptomyc, Pierre Fabre, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, and Daiichi Sankyo; has received personal speaker honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, MSD, PeerVoice, Pfizer, Sanofi, Takeda, and Touch Oncology; has had a board of director role for Grifols; and has received financial support for meeting attendance and/or travel from AstraZeneca, Janssen, and Roche. Dr. Gelsomino has had a consulting or advisory role with Novartis, Eli Lilly, Pfizer, Bristol Myers Squibb, AstraZeneca, and Regeneron. Dr. Goldman has had a consulting or advisory role with AstraZeneca, Bristol Myers Squibb, Lilly, Pfizer, AbbVie, Genentech, Regeneron, Jazz Pharmaceuticals, Gritstone Bio, Turning Point Therapeutics, Puma Biotechnology, and Janssen; and has received research funding from Lilly, Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, AbbVie, Spectrum Pharmaceuticals, Advaxis, and Pfizer. Dr. Hussein has had a consulting or advisory role with AbbVie, Genentech/Roche, CLL Consulting, Tecentriq, Coherus BioSciences, Athenex, Karyopharm Therapeutics, Bristol Myers Squibb, AstraZeneca, Mirati Therapeutics, Exelixis, Ipsen, BeiGene, Aveo, and National Community Oncology Dispensing Association (NCODA); and is president of Florida Society of Clinical Oncology. Dr. M. Johnson has had a consulting or advisory role with Genentech/Roche, AstraZeneca, Merck, Sanofi, Mirati Therapeutics, AbbVie, GSK, Gritstone Bio, Janssen Oncology, Lilly, Amgen, Daiichi Sankyo, Regeneron, Revolution Medicines, Takeda, Alentis Therapeutics, Arcus Biosciences, Biohaven, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio, Fate Therapeutics, Gilead, Hookipa, Immunocore, Jazz, ModeX Therapeutics, Normunity, Novocure, Pfizer, Seagen, Synthekine, and Zai Lab; and has received research funding from EMD Serono, Janssen, Mirati Therapeutics, Genmab, Pfizer, AstraZeneca, Novartis, Array BioPharma, Regeneron, Merck, Hengrui Pharmaceutical, BeiGene, Loxo, AbbVie, Boehringer Ingelheim, Daiichi Sankyo, Sanofi, CytomX Therapeutics, Corvus Pharmaceuticals, Incyte, Genocea Biosciences, Gritstone Bio, Amgen, Genentech/Roche, Adaptimmune, Syndax, Neovia Oncology, Takeda, Shattuck Labs, GSK, Immunocore, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, BerGenBio, Calithera Biosciences, Tmunity Therapeutics Inc., Seven and Eight Biopharmaceuticals, Rubius Therapeutics, Curis, Silicon Therapeutics, Dracen, PMV Pharma, Artios, BioAtla, Elicio Therapeutics, Erasca Inc., Harpoon, Helsinn Healthcare, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Memorial Sloan Kettering Cancer Center, NeoImmuneTech, Numab, Relay Therapeutics, Revolution Medicines, Tempest Therapeutics, Tizona Therapeutics Inc., Turning Point Therapeutics, Vyriad, Y-mAbs Therapeutics, Exelixis, Fate Therapeutics, Merus, Black Diamond Therapeutics, Kartos Therapeutics, Carisma Therapeutics, Rain Therapeutics, Nuvalent, Palleon Pharmaceuticals, EQRx, Immunitas, ArriVent BioPharma, Bayer, Bristol Myers Squibb, City of Hope, Conjupro Biotherapeutics, Immuneering Corporation, Impact Therapeutics, LockBody, Mythic Therapeutics, Neovia Oncology, NextPoint Therapeutics, OncoC4, Rascal Therapeutics, Systimmune, Taiho Oncology, Theras, and Vividion. Dr. Marrone has had a consulting or advisory role with AstraZeneca, Amgen, Bristol Myers Squibb, Janssen, Daiichi Sankyo, Regeneron, and Merus; and has received research funding from Bristol Myers Squibb. Dr. Morgensztern has had a consulting or advisory role with AbbVie, G1 Therapeutics, Lilly Medical, Mirati Therapeutics, Arcus Biosciences, Bayer, Boehringer Ingelheim, Tubulis, Johnson & Johnson, and Natera; and has received research funding from Heat Biologics, Merck, Celgene, AstraZeneca, Baxter, Incyte, AbbVie, Bristol Myers Squibb, EpicentRx, Pfizer, Roche, Lilly, Altum Pharmaceuticals, Array BioPharma, Surface Oncology, Arcus Biosciences, Boehringer Ingelheim, and Y-mAbs Therapeutics. Dr. Nadal has had a consulting or advisory role with MSD, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Pfizer, Takeda, AstraZeneca, Lilly, Amgen, Sanofi, Merck Serono, Janssen Oncology, Qiagen, Daiichi Sankyo, Genmab, Apollomics, and Pierre Fabre; has received research funding from Roche, Pfizer, Bristol Myers Squibb, and Merck Serono; and has received other expenses from MSD, Bristol Myers Squibb, Pfizer, Roche, and Lilly. Dr. Negrao has received research funding to institution from Lilly, Mirati, Bristol Myers Squibb, Novartis, Checkmate, Alaunos, AstraZeneca, Pfizer, Genentech, and Navire; has had a consultant or advisory role with Genentech, Mirati, Merck/MSD, Novartis, Sanofi, Pfizer, Lilly, and AstraZeneca; has had a speakers' bureau role for OncLive, Ideology, BIO Brasil, Medscape, DAVA Oncology, and Targeted Oncology; has received travel expenses from Ideology, DAVA Oncology, and Targeted Oncology; and has received writing support from ApotheCom and Ashfield Healthcare. Dr. Offin has received honoraria from OncLive, American Society for Radiation Oncology, Pfizer, and Targeted Oncology; has had a consulting or advisory role with Novartis, Jazz Pharmaceuticals, the U.S. Department of Defense, and Pfizer; has received travel accommodations and expenses from DAVA Oncology and the International Association for the Study of Lung Cancer; has received research funding from the Druckenmiller Foundation, LUNGevity Foundation, and the U.S. Department of Defense; and has a had a role with Mesothelioma Applied Research Foundation. Dr. Provencio has had a consulting or advisory role with Bristol Myers Squibb, Roche, MSD, AstraZeneca, Takeda, Lilly, Janssen Oncology, Pfizer, and Merck; has had a speakers’ bureau role for Bristol Myers Squibb, Roche, AstraZeneca, MSD, and Takeda; has received research funding from Pierre Fabre, Roche, Boehringer Ingelheim, and Bristol Myers Squibb (institution); and has received other expenses from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Roche, Pierre Fabre, Takeda, and MSD. Dr. Ramalingam has received research funding from Pfizer. Dr. Sanborn has received honoraria from AstraZeneca, GameOn!, Illumina, OncLive, and Targeted Oncology; has had a consulting or advisory role with Amgen, AstraZeneca, EMD Serono, Daiichi Sankyo, G1 Therapeutics, GE HealthCare, Gilead, GSK, Janssen Oncology, Regeneron, and Sanofi Aventis; and has received research funding from Bristol Myers Squibb, Merck, and AstraZeneca. Dr. Smit has received honoraria from Daiichi Sankyo and Boehringer Ingelheim; and has had a consulting or advisory role with Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck, MSD Oncology, Takeda, Daiichi Sankyo, Janssen, Sanofi, Pfizer, DSI DSMB, Taiho DSMB, and Mythic DSMB. Dr. Tsao has had a consulting or advisory role with Novartis, Boehringer Ingelheim, Genentech/Roche, Lilly, Bristol Myers Squibb, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, and Heron; and has received research funding from Merck, Genentech/Roche, Seagen, Millennium, Bristol Myers Squibb, Boehringer Ingelheim, Polaris, EMD Serono, and Takeda. Dr. B.E. Johnson has had a consulting or advisory role with Novartis, Daiichi Sankyo, Checkpoint Therapeutics, G1 Therapeutics, Jazz Pharmaceuticals, GSK, Genentech, AstraZeneca, Hummingbird Diagnostics, BlueDot, Merus NV, Abdera Therapeutics, and Simcere. Usari, Alcasid, Dr. Wilner, Dr. Tonkovyd, and Dr. Zhang are employees of and own stock in Pfizer. The remaining authors declare no conflict of interest.

References

    1. Riely GJ, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non-small-cell lung cancer. J Clin Oncol. 2023;41(21):3700–3711. 10.1200/jco.23.00774 - DOI - PubMed
    1. Planchard D, Sanborn RE, Negrao MV, Vaishnavi A, Smit EF. BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape. NPJ Precis Oncol. 2024;8(1):90. 10.1038/s41698-024-00552-7 - DOI - PMC - PubMed
    1. US Food and Drug Administration. FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation. Accessed November 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-appro....
    1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed February 28, 2025. To view the most recent complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
    1. Hendriks LE, Kerr KM, Menis J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):339–357. 10.1016/j.annonc.2022.12.009 - DOI - PubMed

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