LBA56 - Updated efficacy and safety from the phase II PHAROS study of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC)

Background

Primary analysis of the PHAROS study showed efficacy and safety of encorafenib (enco; BRAF inhibitor) plus binimetinib (bini; MEK inhibitor) in patients (pts) with BRAF V600E-mutant mNSCLC. The primary endpoint was met, with an objective response rate (ORR) by independent review radiology (IRR) of 75% in treatment-naïve and 46% in previously treated pts. Based on these results, the FDA approved enco+bini in 2023 for pts with BRAF V600E-mutant mNSCLC. We report updated results after 18 mo of additional follow-up.

Methods

PHAROS, an ongoing open-label, single-arm, phase 2 study, enrolled 98 pts with BRAF V600E-mutant mNSCLC who were treatment naïve or had received 1 prior systemic therapy. Pts received enco 450 mg once daily and bini 45 mg twice daily. The primary endpoint was ORR by IRR; secondary endpoints included time to response (TTR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results

At the data cutoff, 11 (19%) of 59 treatment-naïve and 4 (10%) of 39 previously treated pts were still receiving enco+bini; median enco+bini treatment duration was 16.3 and 5.5 mo, respectively. Results of the primary and current analyses are shown in the table. At a median follow-up of 33.3 mo, median PFS was 30.2 mo (95% CI 15.7, not estimable [NE]) and median DOR was 40.0 mo (95% CI 23.1, NE) in treatment-naïve pts. Median OS (95% CI) was still NE (31.3 mo, NE) in treatment-naïve and 22.7 mo (14.1, 32.2) in previously treated pts. Nausea, diarrhea, and fatigue remained the most common (>30%) treatment-related adverse events (TRAEs). The safety profile was consistent with that observed in the primary analysis. Table: LBA56

^aExcept OS.1. Riely GJ, et al. J Clin Oncol. 2023;41:3700-11.

Conclusions

After an additional 18 mo of follow-up, enco+bini showed prolonged efficacy, especially in treatment-naïve pts, with a manageable safety profile in pts with BRAF V600E-mutant mNSCLC.

Clinical trial identification

NCT03915951.

Editorial acknowledgement

Medical writing support was provided by Caitlin Cash, PhD, of Nucleus Global and was funded by Pfizer.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

G.J. Riely: Financial Interests, Institutional, Funding: Novartis, Roche/Genentech, Mirati Therapeutics, Merck, Takea, Lilly, Pfizer, Rain Therapeutics; Other, Personal, Other, Travel, accommodations, and other expenses: Bayer, Merck; Non-Financial Interests, Personal, Steering Committee Member: Pfizer, Roche/Genentech, Takeda, Mirati Therapeutics; Non-Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Takeda, Amgen, Daiichi Sankyo, Pfizer, MSD, Merck, Alpha pharmaceutical, Genexin, Voronoi, Yuhan, Gilead, Roche; Financial Interests, Invited Speaker: AstraZeneca, Takeda, Amgen, Daiichi Sankyo, Pfizer, MSD, Merck, Genexin, Voronoi, Yuhan, Roche. J. Clarke: Financial Interests, Personal, Advisory Board: BMS, Coherus, Black Diamond, CDR Life, AstraZeneca, Sanofi, Corbus, Merck, Janssen; Financial Interests, Personal, Other, DSMB: Biothera, G1; Other, Research Grant: Bristol Myers Squibb, Genentech, Spectrum, Adaptimmune, AbbVie, Moderna, GSK, Array, AstraZeneca, Grid Therapeutics, Abel Zeta, AbbVie; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; Non-Financial Interests, Personal, Steering Committee Member: Amgen. I. Dagogo-Jack: Financial Interests, Other, Honoraria: Foundation Medicine, Creative Education Concepts, OncLive, ASCO Post, Dava Oncology, Medscape, Research to Practice, Total Health, Aptitude Health, American Lung Association, PeerView; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Bayer, BostonGene, Bristol Myers Squibb, Catalyst, Genentech, Gilead, Janssen, Eli Lilly, Merus, Novocure, Pfizer, Roche, Sanofi-Genzyme, Syros, ThermoFisher Scientific, Xcovery; Financial Interests, Research Funding: Array, Genentech, Novartis, Pfizer, Guardant Health; Financial Interests, Other, Travel support: Array, Novocure, Pfizer. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer, Genmab; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Local PI: Nuvalent; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. F. Gelsomino: Financial Interests, Personal, Advisory Role: BMS, Eli-Lilly, Novartis, Regeneron, Pfizer. J.W. Goldman: Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca, Bristol Myers Squibb, Lilly, Pfizer, AbbVie, Genentech, Regeneron, Jazz Pharmaceuticals, Gritstone Bio, Turning Point Therapeutics, Puma Biotechnology, Janssen; Financial Interests, Institutional, Research Funding: Lilly, Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, AbbVie, Spectrum Pharmaceuticals, Advaxis, Pfizer. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie, BMS, AZ, Ipsen. M.L. Johnson: Financial Interests, Institutional, Research Funding: AbbVie, Adaptimmune, Amgen, Arcus Biosciences, Array BioPharma, ArriVent BioPharma, Artios Pharma, AstraZeneca, Bayer, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, City of Hope National Medical Center, Conjupro Biotherapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Harpoon, Helsinn Healthcare, Hengrui Therapeutics, Hutchinson MediPharma, Ideaya Biosciences, IGM Biosciences, Immuneering Corporation, Immunitas Therapeutics, Immunocore, Impact Therapeutics, Incyte, Janssen, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, NextPoint Therapeutics, Novartis, Numab Therapeutics, Nuvalent, OncoC4, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Summit Therapeutics, Syndax Pharmaceuticals, Systimmune, Taiho Oncology, Takeda Pharmaceuticals, TCR2 Therapeutics, Tempest Therapeutics, TheRas, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, Vividion, Vyriad, Y-mAbs Therapeutics; Financial Interests, Institutional, Speaker, Consultant, Advisor: AbbVie, Alentis Therapeutics, Amgen, Arucs Biosciences, Arrivent, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Genmab, Gilead Sciences, GSK, Gritstone Oncology, Hookipa Biotech, Immunocore, Janssen, Jazz Pharmaceuticals, Lilly, Merck, Mirati Therapeutics, ModeX Therapeutics, Molecular Axiom, Normunity, Novartis, Novocure, Pfizer, Pyramid Biosciences, Revolution Medicines, Sanofi-Aventis, Seagen, Synthekine, Takeda Pharmaceuticals, Zai Laboratory. D. Morgensztern: Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb/Medarex, Abbott Laboratories; Financial Interests, Personal, Advisory Role, Consulting: AbbVie, G1 Therapeutics, Lilly Medical, Mirati Therapeutics, Arcus Biosciences; Financial Interests, Institutional, Research Funding: 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, Y-mAbs Therapeutics. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Pfizer, Roche, Apollomics, Transgene; Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). M.D. Offin: Non-Financial Interests, Personal, Advisory Role: Mesothelioma Applied Research Foundation, Therapeutics; Non-Financial Interests, Personal, Advisory Board: Black Diamond; Other, Personal, Advisory Role, Honorarium: Novartis, Jazz, Pfizer; Other, Personal, Funding, Grant: Druckenmiller foundation, LUNGevity Foundation, Department of Defense; Other, Personal, Invited Speaker, Honorarium: Targeted Oncology, OncLive, American Society for Radiation Oncology. M. Provencio Pulla: Financial Interests, Personal and Institutional, Advisory Board: Amgen, Pfizer, Daiichi Sankyo, Johnson & Johnson, BMS, Takeda, AstraZeneca, Gilead, MSD, Guardant Health, Ipsen, Incyte Biosciences, Bayer; Financial Interests, Personal and Institutional, Invited Speaker: BMS, AstraZeneca, MSD, Roche, Takeda, Eli Lilly, F. 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Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD, Boehringer Ingelheim, Roche, Eli Lilly, Takeda, Sanofi, Janssen, BMS; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Seranno; Financial Interests, Institutional, Other, DSMB member: DSI; Financial Interests, Institutional, Local PI: Pfizer, AZ, Genmab, DSI, Sanofi. A.S. Tsao: Financial Interests, Personal, Speaker, Consultant, Advisor: Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, EMD Serono, Genentech, GSK, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, Inc., Summit Therapeutics, Novocure, Merck Research Laboratories and the Office of the Chief Medical Officer Grants, Bristol Myers Squibb Company; Financial Interests, Personal, Sponsor/Funding: Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Epizyme, Genetech, Merck, Millemmium, Novartis, Polaris Partners, Seattle Genetics, Bristol Myers Squibb Company, Genentech. A. Alcasid: Financial Interests, Full or part-time Employment: Pfizer; Financial Interests, Stocks or ownership: Pfizer. T. Usari: Financial Interests, Full or part-time Employment: Pfizer; Financial Interests, Stocks or ownership: Pfizer, Viatris. K. Wilner: Financial Interests, Full or part-time Employment: Pfizer Inc; Financial Interests, Stocks or ownership: Pfizer Inc. B. Johnson: Financial Interests, Royalties: DFCI; Financial Interests, Speaker, Consultant, Advisor: Novartis, Checkpoint Therapeutics, AstraZeneca, Daichi Sankyo, Genentech, Bluedot Bio, Jazz Pharmaceuticals, Merus, Abdera, Simcere Pharmaceutical; Financial Interests, Member, Data Safety Monitoring Committee: Revolution Medicine, Merck; Non-Financial Interests, Steering Committee Member: Pfizer.