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.
Year: 2025
Type: conference-abstract
Study design: Study Protocol
Abstract: TPS1127 Background: Endocrine therapy (ET) plus a CDK4/6i is the mainstay treatment in first-line ER+/HER2- mBC; however, a subset of patients 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 patients during prolonged aromatase inhibitor therapy in mBC. In the phase 3 EMERALD trial, elacestrant significantly prolonged PFS vs standard-of-care (SOC) ET and was associated with a manageable safety profile in patients with ER+/HER2- 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 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 patients with ESR1 -mut tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) [Bidard, 2022]. Preclinical studies demonstrated that elacestrant 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, elacestrant may improve clinical outcomes in CDK4/6i-naïve patients and provide a convenient all-oral treatment option if combined with CDK4/6i. The ELCIN trial will evaluate efficacy and safety of elacestrant in patients with ER+/HER2- mBC who received prior ET and no prior CDK4/6i in the metastatic setting. Methods: ELCIN (NCT05596409) is an open-label, multicenter, single-arm phase 2 trial. Eligible patients are women or men with ER+/HER2− mBC who received 1-2 lines of prior ET and no prior CDK4/6i or chemo in the metastatic setting. Patients 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. Patients will receive elacestrant 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 elacestrant 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 patients; recruitment is ongoing worldwide. Clinical trial information: NCT05596409 .
Source: Journal of Clinical Oncology
Institutions: The University of Texas at San Antonio Health Science Center, Institute of Oncology Prof. Dr. Ion Chiricuta, Comprehensive Cancer Centers of Nevada, Latin American Cooperative Oncology Group (LACOG), Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Menarini Group (Italy), Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Menarini Group
OpenAlex ID: W4410805161