Abstract CT255: ELEGANT: Elacestrant versus standard endocrine therapy (ET) in women and men with node-positive, estrogen receptor-positive (ER+), HER2-negative (HER2-), early breast cancer (eBC) with high risk of recurrence in a global, multicenter,

Abstract Background: Adjuvant (adj) ET is the standard of care (SOC) for treating ER+/HER2- eBC. Despite advances to optimize adj treatment in high-risk ER+/HER2- eBC, there continues to be a risk of local and metastatic (incurable) recurrence that persists, and new therapies with desirable safety profiles are warranted. Elacestrant is a next-generation oral SERD that provides a novel MOA that has shown both SERD (degradative) and SERM (partial agonist) activity that differs from currently available adj ET (Wardell, ERC 2015). In the EMERALD trial, elacestrant significantly prolonged PFS vs SOC ET in the overall population (HR 0.70; 95% CI 0.55-0.88; P=0.0018) and in pts with ESR1-mut tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) (Bidard, JCO 2022). In pts with ESR1-mut tumors who received prior ET+CDK4/6i ≥12 mo, mPFS with elacestrant was 8.6 vs 1.9 mo with SOC ET (Bardia, CCR 2024). In a preoperative, window of opportunity ER+/HER2- eBC trial (SOLTI-1905-ELIPSE), elacestrant was associated with complete cell cycle arrest (defined as Ki67<2.7%) rate of 27% and a statistically significant mean change from baseline, shifting tumor biology toward a more endocrine-sensitive and less proliferative tumor phenotype. Given that elacestrant demonstrated efficacy in mBC regardless of ESR1-mut status relative to SOC ET and has shown biologic activity in eBC, it is hypothesized that elacestrant can prolong invasive breast cancer-free survival (IBCFS) in pts with high-risk eBC who received prior adj ET±CDK4/6i. Design and Methods: ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in pts with eBC and a high risk of recurrence. Pts will be randomized 1:1 to continue SOC ET or to elacestrant for a duration of 5 yrs. Eligible pts are women or men with ER+/HER2− node-positive eBC who have completed 24-60 mo of adj ET±CDK4/6i, & ECOG PS ≤1. Pts who received a prior CDK4/6i or a PARP inhibitor must have already completed or discontinued these treatments. Pre/perimenopausal women and men will be administered a LHRH agonist. Exclusion criteria include inflammatory breast cancer, history of prior invasive breast cancer, and >6 mo continuous interruption of prior SOC adj ET or discontinuation of adj ET >6 mo prior to randomization. The primary endpoint is IBCFS. Key secondary endpoints include DRFS, OS, IDFS, safety, PROs-QoL, and PK. Status: Planned enrollment is 4,220 patients; recruitment is ongoing. Citation Format: Aditya Bardia, Virginia Kaklamani, Joyce O’Shaughnessy, Peter Schmid, J. Thaddeus Beck, Michelino De Laurentiis, Giuseppe Curigliano, Hope S. Rugo, Carlos H. Barcenas, William J. Gradishar, Michail Ignatiadis, David A. Cameron, Giulia Tonini, Simona Scartoni, Jennifer Crozier, Leo Viana Nicacio, Tomer Wasserman, Sara M. Tolaney. ELEGANT: Elacestrant versus standard endocrine therapy (ET) in women and men with node-positive, estrogen receptor-positive (ER+), HER2-negative (HER2-), early breast cancer (eBC) with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT255.