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.

TPS1127Background: 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.