Abstract OT2-11-07: Solti-1905. Elacestrant in preoperative setting, a window of opportunity study (ELIPSE trial)
Authors: Vidal María , Muñoz Montserrat , Margeli Mireia , González Xavier , Amillano Kepa , Sánchez-Bayona Rodrigo , Salvador Fernando , Pascual Tomás , Prat Aleix , Bellet Meritxell 
Published: March 2022

Background.Patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) are mainly treated with therapies that target estrogen receptor (ER) signaling to impair tumor cell proliferation. Several drugs targeting the ER pathway are currently used in the clinical practice including aromatase inhibitors (AI) that limit the production of estradiol, selective ER modulators (SERMs) that compete with estradiol for binding ER, and selective ER degraders (SERDs) that induce ER degradation. Despite the availability of these drugs, finding new ET remains a clinical unmet need since some patients do not initially respond to these treatments or become resistant to available endocrine agents. Elacestrant is an orally bioavailable drug that acts as SERD in breast tissue promoting degradation of ER and inhibiting breast cancer cell proliferation. Several clinical studies have confirmed the tolerable safety profile of elacestrant in BC (Bardia A et al. ASCO, 2021) and a phase III trial investigating elacestrant versus standard ET in metastatic BC patients is ongoing for patients treated with at least 1 prior ET and a CDK4/6 inhibitor for advanced BC (EMERALD; NCT03778931). In this study, we aim to investigate the biological effect of elacestrant on cell proliferation in patients with ER+/HER2- resectable BC. Study design. ELIPSE is prospective, multicenter, single-arm, window-of-opportunity study designed to evaluate the biological effect of elacestrant in treatment naïve patients with ER+/HER2- resectable BC. The study population consists of postmenopausal women with clinically negative axillary lymph node (cN0) and whose primary tumors are≥ 1.5 cm by ultrasound with Ki67 ≥10% locally assessed. Patients will receive 400 mg of elacestrant in monotherapy orally, once a day, continuously. After 4 weeks of treatment, surgery will be performed in accordance with local practice. Two biopsies of the same lesion will be obtained as mandatory: a baseline sample and a surgical sample (tumor core-biopsy is permitted if surgery is not performed after 4 weeks of treatment). Plasma samples for biomarkers will be collected at baseline, surgery and end of study visit. The primary objective is to evaluate the Complete Cell Cycle Arrest rate (defined as Ki67 ≤ 2.7%) by central assessment after 4 weeks of elacestrant therapy. Secondary endpoints include:. 1) safety,. 2) correlation of biological activity determined by changes in: Ki67 as a continuous variable, intrinsic PAM50 subtypes, proliferative signatures, tumor cellularity and tumor-infiltrating lymphocytes (CelTIL, Nuciforo P et al., Ann Oncol, 2018) in tumor samples taken before and at the end of treatment, and. 3) analysis of ctDNA dynamics after treatment. As of July 2021, 7 patients have been enrolled in 4 sites in Spain. NCT04797728. Acknowledgement. This study is financially supported by Radius Pharmaceuticals, Inc.

Citation Format: María Vidal, Montserrat Muñoz, Mireia Margeli, Xavier González, Kepa Amillano, Rodrigo Sánchez-Bayona, Fernando Salvador, Tomás Pascual, Aleix Prat, Meritxell Bellet. Solti-1905. Elacestrant in preoperative setting, a window of opportunity study (ELIPSE trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-07.