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, ope

TPS619 Background: Adjuvant ET is the standard of care (SOC) for treating ER+/HER2- eBC. Despite advances to optimize adjuvant 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 mechanism of action that has shown both SERD (degradative) and SERM (partial agonist) activity that differs from currently available adjuvant 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 patients with ESR1 -mut tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) (Bidard, JCO 2022). In patients 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 (Vidal, CCR 2025). 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 patients with high-risk eBC who received prior adjuvant ET±CDK4/6i. Methods: ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in patients with eBC and a high risk of recurrence. Patients will be randomized 1:1 to continue SOC ET or to elacestrant for a duration of 5 yrs. Eligible patients are women or men with ER+/HER2− node-positive eBC who have completed 24-60 mo of adjuvant ET±CDK4/6i and have ECOG PS ≤1. Patients 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 adjuvant ET or discontinuation of adjuvant ET >6 mo prior to randomization. The primary endpoint is IBCFS. Key secondary endpoints include distant relapse-free survival, overall survival, invasive disease-free survival, safety, patient-reported outcomes-quality of life, and pharmacokinetics. Status: Planned enrollment is 4,220 patients; recruitment is ongoing. Clinical trial information: NCT06492616 .