Abstract P2-08-20: ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study

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Abstract Background: Endocrine therapy plus a CDK4/6 inhibitor (ET+CDK4/6i) is the mainstay treatment in first-line ER+/HER2- mBC; however, a subset of patients is unable to tolerate CDK4/6i, and resistance to ET arises. Intrinsic resistance mechanisms include alterations in the PI3K/AKT/mTOR or cell cycle pathways; acquired resistance mechanisms include estrogen receptor gene alpha (ESR1)-mut developing during ET in mBC. In EMERALD, single-agent elacestrant significantly prolonged progression-free survival (PFS) vs standard-of-care (SOC) ET and was associated with a manageable safety profile in patients with ER+/HER2- advanced or mBC previously treated with ET+CDK4/6i, leading to its approval as the first clinically available oral SERD. Elacestrant significantly reduced the risk of progression or death compared with SOC ET by 30% in the overall population (HR = 0.70; 95% CI, 0.55 to 0.88; P = 0.002) and by 45% in patients with ESR1-mutated tumors (HR = 0.55; 95% CI, 0.39 to 0.77; P = 0.0005) [Bidard, 2022]. To provide an option for patients unable to receive CDK4/6i and address resistance, the ELCIN trial aims to evaluate the efficacy and safety of elacestrant in patients with ER+/HER2- mBC who received prior ET but did not receive a prior CDK4/6i in the metastatic setting. Methods: ELCIN (NCT05596409) is a single-arm phase 2 trial. Eligible patients are women or men with ER+/HER2− mBC who received 1-2 prior ET and no prior CDK4/6i or chemotherapy in the metastatic setting. Patients must have measurable disease per RECIST v1.1 or ≥1 lytic or mainly lytic bone lesion (in patients with bone disease only), ECOG PS ≤1, and no active or newly diagnosed central nervous system metastases. Patients will receive elacestrant 345 mg (400 mg elacestrant hydrochloride) once daily. The primary endpoint is investigator-assessed progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), overall survival (OS), patient-reported outcomes (PROs), health-related quality of life (HRQoL), and safety. Exploratory endpoints include assessing elacestrant efficacy according to ESR1-mutation status at baseline, assessing changes in biomarkers, including allele mutation frequencies in cell-free nucleic acids (cfNAs) in blood and the relationship between efficacy endpoints and allele mutation frequencies (at baseline and post-baseline). ELCIN has a planned sample size of 60 patients; recruitment is ongoing worldwide. Citation Format: Virginia Kaklamani, Giorgi Dzagnidze, Nicoleta Zenovia Antone, Anu R. Thummala, Mikheil Janjalia, Patricia Santi, Carlos Barrios, Mehmet Ali Nahit Sendur, Xiaoling Zhang, Angela Gambioli, Manuel Dominguez, Kathy Puyana Theall, Tomer Wasserman, William J. Gradishar. ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-08-20.

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