73TiP - Global phase III studies evaluating vepdegestrant in estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer: VERITAC-2 and VERITAC-3

Background

Vepdegestrant (ARV-471) is an oral PROteolysis TArgeting Chimera (PROTAC) ER degrader. In a first-in-human phase 1/2 study (NCT04072952), vepdegestrant monotherapy was well tolerated with clinical activity in heavily pretreated patients (pts) with ER+/HER2- advanced breast cancer. Phase 1 studies (NCT05463952; NCT05732428) are evaluating vepdegestrant safety and pharmacokinetics in pts with ER+/HER2- advanced breast cancer in Japan and China, respectively. In global, randomized phase 3 studies with sites in the Asia-Pacific region, vepdegestrant is being evaluated as 2nd/3rd-line monotherapy (VERITAC-2; NCT05654623) and as 1st-line therapy plus palbociclib (VERITAC-3; NCT05909397).

Trial design

VERITAC-2 is comparing vepdegestrant vs fulvestrant in pts with ER+/HER2- locoregional recurrent/metastatic breast cancer; 1 prior line of cyclin-dependent kinase (CDK)4/6 inhibitor therapy combined with endocrine therapy (ET); ≤1 additional line of ET; most recent ET given for ≥6 months before disease progression; and disease progression during/after last line of therapy. Pts (N≈560) are randomized 1:1 to oral vepdegestrant 200 mg once daily (QD) or intramuscular fulvestrant. The primary endpoint is progression-free survival (PFS) by blinded independent central review (BICR). VERITAC-3 will compare vepdegestrant + palbociclib vs letrozole + palbociclib as 1st-line treatment in pts with ER+/HER2- locoregional recurrent/metastatic breast cancer; no prior treatment in the advanced setting; and no prior treatment in any setting with CDK4/6 inhibitors, vepdegestrant, fulvestrant, elacestrant, or other investigational agents. To select the dose of palbociclib for the phase 3 portion of the study, pts (N≈50) will be randomized 1:1 in an open-label study lead-in to vepdegestrant 200 mg QD + palbociclib 100 mg QD or 75 mg QD. The phase 3 dose of palbociclib will be determined based on incidence of grade 4 neutropenia, study drug dose reduction, and study drug discontinuation in the first 4 cycles. In the phase 3 portion, pts (N≈1130) will be randomized to vepdegestrant + palbociclib or letrozole + palbociclib. The primary endpoint is PFS by BICR.

Clinical trial identification

NCT05654623 (VERITAC-2); NCT05909397 (VERITAC-3).

Legal entity responsible for the study

Arvinas Estrogen Receptor, Inc.

Funding

Arvinas Estrogen Receptor, Inc.

Disclosure

H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Steering Committee Member: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Novartis, Pfizer, Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Local PI: Lilly, Bayer, Nihon Kayaku, Behringer. E.P. 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, AstraZeneca, Daiichi Sankyo, SeaGen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, 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, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Bliss BioPharmaceuticals, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Loxo Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics. C.X. Ma: Financial Interests, Personal, Advisory Board: Agendia, Bayer Healthcare Pharmaceuticals, Eli Lilly & Co., Sanofi - Genzyme, RayzeBio Inc.; Financial Interests, Personal, Advisory Board, Also Consulting Services: AstraZeneca Pharmaceuticals LP; Financial Interests, Personal, Other, Consulting Services - review data for oral paclitaxel.: Athenex; Financial Interests, Personal, Invited Speaker: Guardant Health, PlusOne Health GmbH; Financial Interests, Personal, Advisory Board, And Consulting Services: Novartis Pharma AG, Olaris Inc., Tempus; Financial Interests, Personal, Other, Consulting Services: Pfizer, Seattle Genetics Inc., Sermonix Pharmaceuticals; Non-Financial Interests, Personal, Other, Consulting Services: Medical Pharma Services Inc.; Financial Interests, Personal, Royalties, Authorship Royalties, co-author: UptoDate; Financial Interests, Personal and Institutional, Coordinating PI: Pfizer Inc. M. De Laurentiis: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: Roche, Novartis, Pfizer, Eli Lilly, Amgen, AstraZeneca, MSD, Pierre Fabre, Seattle Genetics, Gilead Sciences, Ipsen. S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options, axis medical, cancer expert now, ICHE, MJH Associates, PER, Primo, Projects in Knowledge, Prova Education, Research to Practice, Ultimate Medical Academy, Vaniam, WebMD, Peer Education, PrecisCA; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Local PI: Ambrx, AstraZeneca, Arvinas, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, Sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, orinove, Orum; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, Celcuity; Financial Interests, Institutional, Research Grant: Samumed, Ambrx; Financial Interests, Personal, Steering Committee Member: Greenwich Life Sciences, Orum; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead; Non-Financial Interests, Personal, Principal Investigator: Daiichi Sankyo, Genentech, Seattle Genetics; Non-Financial Interests, Personal, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network; Non-Financial Interests, Personal, Member: ASCO, AACR; Non-Financial Interests, Personal, Other, speaker: National Breast Cancer Coalition. S.A. Wander: Financial Interests, Personal, Advisory Board: Foundation Medicine, Veracyte, Hologic, Biovica, Eli Lilly, Pfizer, Puma Biotechnology; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker: 2ndMD, Eli Lilly, Guardant Health; Financial Interests, Personal, Research Funding: Genentech, Eli Lilly, Pfizer, Nuvation Bio, Regor Therapeutics. M.A. Danso: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: Novartis, Pfizer, Immunomedics, Seattle Genetics; Financial Interests, Personal, Other, Honoraria: Amgen. D.R. Lu: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks or ownership: Pfizer. J. Perkins: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks or ownership: Pfizer; Financial Interests, Personal, Royalties, Patents, Royalties, Other Intellectual Property: Pfizer. Y. Liu, L. Tran, D.Z. Yang: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks or ownership: Pfizer. S. Anderson: Financial Interests, Personal, Full or part-time Employment: Arvinas Operations, Inc; Financial Interests, Personal, Stocks/Shares: Arvinas Operations, Inc. C. Chappey: Financial Interests, Personal, Full or part-time Employment: Pfizer. M. Campone: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Sanofi, Menarini, Gilead, Seagen; Financial Interests, Personal, Invited Speaker: Novartis, Lilly; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Lilly.