Abstract CT236: ELCIN: Elacestrant (Ela) in women and men with CDK4/6 inhibitor (CDK4/6i)- naive estrogen receptor- positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study
Authors: Virginia Kaklamani, Giorgi Dzagnidze, Nicoleta Zenovia Antone, Anu R. Thummala, Mikheil Janjalia, Patricia Santi, Carlos Barrios, Mehmet Ali Sendur, Xiaoling Zhang, Angela Gambioli, Manuel Dominguez, Kathy Puyana Theall, Tomer Wasserman, William J. Gradishar
Journal: Cancer Research (2025)

Abstract Background: Endocrine therapy (ET) plus a CDK4/6i is the mainstay treatment in 1L ER+/HER2- mBC; however, a subset of patients (pts) are unable to tolerate CDK4/6i, and resistance to ET emerges. Intrinsic resistance mechanisms include alterations in the PI3K/AKT/mTOR or cell cycle pathways; acquired resistance mechanisms include estrogen receptor gene 1 mutations (ESR1-mut), which emerge in up to 50% of pts during prolonged aromatase inhibitor therapy in mBC. In the phase 3 EMERALD trial, Ela significantly prolonged PFS vs standard-of-care (SOC) ET and was associated with a manageable safety profile in pts with ER+/HER2- mBC previously treated with ET+CDK4/6i, leading to its approval as the first clinically available oral SERD. Ela significantly reduced the risk of progression or death vs SOC ET by 30% in the overall population (HR 0.70; 95% CI 0.55-0.88; P=0.002) and by 45% in pts with ESR1-mut tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) [Bidard, 2022]. Preclinical studies demonstrated that Ela is equally active in both in vitro and in vivo models of ER+/HER2- breast cancer, regardless of prior exposure to CDK4/6i. Based on preclinical models and clinical efficacy data, Ela may improve clinical outcomes in CDK4/6i-naïve pts and provide a convenient all-oral treatment option if combined with CDK4/6i. The ELCIN trial will evaluate efficacy and safety of Ela in pts with ER+/HER2- mBC who received prior ET and no prior CDK4/6i in the metastatic setting. Design and Methods: ELCIN (NCT05596409) is an open-label, multicenter, single-arm phase 2 trial. Eligible pts are women or men with ER+/HER2− mBC who received 1-2L of prior ET and no prior CDK4/6i or chemo in the metastatic setting. Pts must have measurable disease per RECIST v1.1 or a mainly lytic bone lesion (for bone disease only), ECOG PS ≤1, adequate bone marrow and organ function, and no active or newly diagnosed CNS metastases or visceral crisis. Pts will receive Ela 345 mg once daily. The primary objective is investigator-assessed PFS. Secondary objectives are ORR, DoR, CBR, OS, PROs-QoL, and safety. Exploratory objectives include Ela efficacy according to ESR1-mut status, changes in biomarkers, including allele mutation frequencies (cfNAs), and relationship between efficacy endpoints. Status: ELCIN has a planned sample size of 60 pts; recruitment is ongoing worldwide. Citation Format: Virginia Kaklamani, Giorgi Dzagnidze, Nicoleta Zenovia Antone, Anu R. Thummala, Mikheil Janjalia, Patricia Santi, Carlos Barrios, Mehmet Ali Sendur, Xiaoling Zhang, Angela Gambioli, Manuel Dominguez, Kathy Puyana Theall, Tomer Wasserman, William J. Gradishar. ELCIN: Elacestrant (Ela) in women and men with CDK4/6 inhibitor (CDK4/6i)- naive estrogen receptor- positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 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 CT236.