Abstract OT-09-11: AMEERA-4, a phase 2 window study of SAR439859 vs letrozole in post-menopausal women with newly diagnosed estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer

Background Endocrine therapy targeting estrogen receptor (ER) signaling is the standard of care for women with ER+ breast cancer. Selective ER degraders (SERDs) block ER signaling through dual competitive antagonism and receptor degradation. SAR439859, a potent, oral SERD, is in clinical development for ER+/HER- breast cancer. AMEERA-4 (NCT04191382; ACT16106) is a 14-day preoperative, non-therapeutic ‘window of opportunity’ trial to assess the direct effects of SAR439859 on tumor cell proliferation by evaluating the pharmacodynamic activity of SAR439859 in ER+/HER2- breast cancer. Methods This international, open-label, Phase 2 randomized study evaluates SAR439859 at two dose levels vs the aromatase inhibitor letrozole by assigning 126 preoperative patients 1:1:1 to receive SAR439859 400 mg/day, SAR439859 200 mg/day or letrozole 2.5 mg/day. SAR439859 dosing is based on an ongoing AMEERA-1 Phase 1/2 study (NCT03284957; TED14856) in metastatic breast cancer. Postmenopausal women with ER+/HER2- breast cancer indicated for immediate surgery (Stage I, Stage II or operable Stage III), Eastern Cooperative Oncology Group performance status 0-1, and Ki67 levels of ≥ 15% are eligible. Exclusion criteria include disorders potentially affecting absorption of SAR439859 or letrozole, and any prior therapy for breast cancer. Patients receive study treatment for 14 days, with the last dose given on the day before surgery. Paired tumor biopsies for assessment of biomarkers are performed at baseline and during surgery. The primary study endpoint is change in Ki67, a predictor of treatment benefit and long-term survival outcomes, after 14 days of treatment compared with baseline. Secondary endpoints include proportion of patients with ≥ 50% decrease in Ki67, ER expression to assess degradation, and safety. Pharmacokinetics of SAR439859, additional tumor markers, genomic mutation profile, Preoperative Endocrine Prognostic Index and pathological complete response will also be assessed. The study is currently recruiting. Funding: Sanofi. © 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved. Citation Format: Mario Campone, Christina Herold, Qiuyan Wang, Vasiliki Pelekanou, Sylvaine Cartot-Cotton, Bethany Ling. AMEERA-4, a phase 2 window study of SAR439859 vs letrozole in post-menopausal women with newly diagnosed estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-09-11.