AMEERA-4: A preoperative window-of-opportunity (WOO) study to assess the pharmacodynamic (PD) activity of amcenestrant or letrozole in postmenopausal patients with ER+/HER2− primary breast cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.528
• Publication Date: 2022-06-06T15:51:47Z
• Authors: Mario Campone; Yvonne Dong; Bethany Ling; Lei Wang; Christina Isabell...
• Keywords: Letrozole; Clinical endpoint; Palbociclib; Pharmacodynamics

528 Background: Amcenestrant is an optimized oral selective ER degrader (SERD) that antagonizes and degrades the has demonstrated favorable preliminary safety antitumor activity as monotherapy in combination with palbociclib postmenopausal patients ER+/HER2− advanced breast cancer, irrespective of baseline (BL) ESR1 mutation status. Here we present final results AMEERA-4 (NCT04191382), a Phase 2 preoperative WOO study evaluated PD two dose levels amcenestrant or letrozole using paired biopsies assessed for biomarkers. Methods: Postmenopausal women operable stage I–III (tumor size ≥ 10 mm by ultrasound) cancer Ki67 15% local assessment were randomized 1:1:1 to 400 mg once daily (QD), 200 QD 2.5 14 days before surgery. Antiproliferative activity, measured centrally change from BL after 14-day treatment different doses vs letrozole, was planned primary endpoint. Main secondary endpoints included target engagement, through expression H-Score, safety. Results: Trial enrollment voluntarily stopped early, informative data supporting adjuvant development became available; therefore, no formal statistical comparisons conducted. Among 105 (amcenestrant mg: n = 34, 36, letrozole: 35), 95 treated had available pre- post-treatment per central review (modified ITT population). No major imbalances patient tumor characteristics observed. The geometric least squares means (LSM) estimate (95% CI) reduction 75.9% (67.9, 81.9) mg, 68.2% (58.4, 75.7) 77.7% (70.0, 83.4) letrozole. LSM absolute H-score −176.7 (−201.4, −152.0) −202.9 (−226.1, −179.7) −32.5 (−57.2, −7.7) median relative changes −65.3%, −68.3% −9.5%, respectively. incidence treatment-related adverse events (TRAEs) 21.2% 22.2% 25.7% Grade 3 TRAEs occurred any arm. Conclusions: Both robust reductions, strongly engaged target, continued show profile early population, consistent previous published reports. Based on safety, emerging other ongoing trials, selected our setting; AMEERA-6 (NCT05128773). Clinical trial information: NCT04191382.