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

TPS1153 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 risk of local and metastatic recurrence that persists, 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 ESR1m tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) (Bidard, JCO 2022). In patients with ESR1m 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 patients with ER+/HER2− eBC, the SOLTI-1905-ELIPSE and SOLTI-2104-PremiERe trials showed that preoperative elacestrant was associated with a statistically significant mean change of complete cell cycle arrest rate and led to a shift in tumor biology towards a more endocrine-sensitive and less proliferative tumor phenotype in both pre- and post-menopausal women (Vidal, CCR 2025; Bellet, SABCS 2025). Given that elacestrant demonstrated efficacy in mBC regardless of ESR1m 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 Ph3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in patients with eBC and high risk of recurrence. Patients will be randomized 1:1 to continue SOC ET or to elacestrant for a duration of 5 years. Eligible patients are women/men with ER+/HER2− node-positive eBC who received between 2-5 years of SOC ET±CDK4/6i and have ECOG PS ≤1. Patients who received a prior CDK4/6i or PARP inhibitor must have completed or discontinued these treatments. Pre/perimenopausal women and men will be administered a LHRH agonist. Exclusion criteria include stage IV mBC, inflammatory BC, history of prior invasive BC, history of malignancy within 3 years of randomization date, >6 mo continuous interruption of prior SOC adjuvant ET or discontinuation of adjuvant ET >6 mo prior to randomization, and received prior treatment with SERDs. The primary objective is IBCFS. Key secondary objectives are distant relapse-free survival, overall survival, invasive disease-free survival, safety, PROs-QoL, and PK. Planned enrollment is 4,220 patients; recruitment is ongoing. Clinical trial information: NCT06492616 .