ARV-471 is an oral PROTAC ER degrader that binds to and degrades both wild-type ER and
Eligible pts (aged ≥18 years) have histologically or cytologically confirmed ER+/HER2- metastatic, recurrent, or unresectable breast cancer; received 1–3 prior lines systemic therapy in the advanced/metastatic setting, including ≥1 endocrine therapy and ≤1 chemotherapy; and progression on or intolerance to a CDK4/6 inhibitor. Pts may not have received prior ARV-471 or an mTOR-targeting therapy. ARV-471 combined with everolimus is administered orally in 28-day cycles. The primary endpoints are dose-limiting toxicities to determine the recommended phase II dose for ARV-471 in combination with everolimus, and type, frequency, and severity of adverse events and laboratory abnormalities. Secondary endpoints are preliminary antitumor activity (overall response rate, clinical benefit rate, and duration of response) and pharmacokinetic parameters of ARV-471 plus everolimus.
NCT05501769.
Medical writing support: Justine Lempart, PhD, of Apollo Medical Communications, and funded by Arvinas Operations, Inc.
Arvinas Estrogen Receptor, Inc.
Arvinas Estrogen Receptor, Inc.
A. Schott: Financial Interests, Personal, Other, Contracted Research: Pfizer, Takeda, Genentech, Arvinas; Financial Interests, Personal, Other, Receipt of Intellectual Property Rights/Patent Holder: Imbio, LLC. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp& Dohme, GSK, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. S. Ivie: Financial Interests, Personal, Full or part-time Employment: Arvinas Operations, Inc. R. Gedrich: Financial Interests, Personal, Full or part-time Employment: Arvinas Operations, Inc.; Financial Interests, Personal, Stocks/Shares: Arvinas Operations, Inc. E. Zhi: Financial Interests, Personal, Full or part-time Employment: Arvinas; Financial Interests, Personal, Stocks/Shares: Arvinas; Financial Interests, Personal, Project Lead: Arvinas. J. Ranciato: Financial Interests, Personal, Full or part-time Employment: Arvinas. J. Perkins: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Other, Patent Holder: Pfizer. E. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, Arcus, AstraZeneca, Daiichi Sankyo, Seagen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Immunomedics, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, InventisBio, Verastem, eFFECTOR Therapeutics, CytomX, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Jacobio, Atlas MedX, Ellipses, Incyte, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Cascadian Therapeutics, Artios, BeiGene, Bliss BioPharmaceuticals, Context Therapeutics, Cullinan-Florentine, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Relay Therapeutics, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Tolmar, Torque Therapeutics. All other authors have declared no conflicts of interest.