The orally administered PROTAC ER degrader ARV-471 demonstrated potent ER degradation and tumor growth inhibition, including tumor regression, in preclinical models. In the first-in-human phase I/II study, once-daily (QD) ARV-471 monotherapy was well tolerated and showed antitumor activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. Anastrozole, an aromatase inhibitor, is a standard treatment option for patients with ER+/HER2- localized breast cancer. Here we describe an open-label, randomized, noncomparative, multi-country phase II study (NCT05549505) to evaluate the safety and clinical activity of ARV-471 or anastrozole in patients with breast cancer amenable to definitive surgical resection.
The following patients are eligible for TACTIVE-N (N∼150): postmenopausal women (aged ≥18 years) with histologically or cytologically confirmed ER+/HER2- localized breast cancer with ER staining of ≥10% of tumor cell nuclei (Ki-67 score ≥5%, clinical T1c-T4c, N0-N2, M0 breast cancer). Patients with bilateral breast ductal carcinoma in situ, bilateral invasive breast cancer, or prior treatment for breast cancer are excluded. Patients will be randomized to receive ARV-471 or anastrozole orally QD until surgical resection approximately 5.5 months after starting treatment (cycle 6, day 18 ± 10 days). The primary objective is to evaluate the effect of ARV-471 or anastrozole on Ki-67 expression in tumors after 2 weeks of treatment. Secondary objectives include safety, pathological response (pathologic stage, pathologic complete response rate, and modified preoperative endocrine prognostic index score at the time of surgical resection), and clinical response (breast-conserving surgery rate, radiographic response rate during cycle 6, and best percentage change in caliper measurement on cycle 6 day 1).
NCT05549505.
Medical Writing Support: Beth Sesler, PhD, of Apollo Medical Communications, and funded by Arvinas Operations, Inc.
Arvinas Estrogen Receptor, Inc.
Arvinas Estrogen Receptor, Inc.
P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. K. Clifton: Financial Interests, Personal, Advisory Board: Biotheranostics, Pfizer; Financial Interests, Personal, Research Grant: Cancer and Aging Research Group; Financial Interests, Institutional, Research Grant: BMS. M. Lachowicz: Financial Interests, Institutional, Full or part-time Employment: Arvinas, Inc; Financial Interests, Institutional, Stocks/Shares: Arvinas; Other, From May 2017 until Feb 2022, I had a full time position as a Physician Assistant at the Yale New Haven Hospital Phase I clinic, which included being a sub-investigator on several Phase I/II Oncology clinical trials.: Yale New Haven Hospital. R. Gedrich: Financial Interests, Personal, Full or part-time Employment: Arvinas; Financial Interests, Personal, Stocks/Shares: Arvinas. J. Ranciato: Financial Interests, Personal, Full or part-time Employment: Arvinas. E. Zhi: Financial Interests, Personal, Full or part-time Employment: Arvinas; Financial Interests, Personal, Stocks/Shares: Arvinas; Financial Interests, Personal, Project Lead: 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. S.A. Hurvitz: Financial Interests, Personal, Research Grant: Ambrx, Amgen, Arvinas, AstraZeneca, Bayer, Cytomx, Daiichi Sankyo, Dantari, Dignitana, Genentech/Roche, G1-Therapeutics, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, OBI Pharma, Orinove, Pfizer, Phoenix Molecular Designs, Ltd., Pieris, PUMA, Radius, Samumed, Sanofi, Seattle Genetics/Seagen, Zymeworks; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca. All other authors have declared no conflicts of interest.