Abstract OT2-01-03: ELEVATE: A phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC)
Authors: Rugo Hope , Bardia Aditya , Cortés Javier , Curigliano Giuseppe , Hamilton Erika , Hurvitz Sara , Loibl Sibylle , Scartoni Simona , Sahmoud Tarek , Grzegorzewski Krzysztof , Habboubi Nassir , O’Shaughnessy Joyce 
Published: March 2023

Abstract
Background: Elacestrant demonstrated significantly prolonged progression-free survival (PFS) and a manageable safety profile compared with standard of care endocrine therapy in the phase 3 EMERALD trial that enrolled patients with estrogen-receptor positive (ER+)/HER2− mBC following disease progression on prior endocrine and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy. Benefit was observed in the overall population and in patients with ESR1 mutations. Combining elacestrant with targeted agents utilized in combination with endocrine therapy in mBC is of therapeutic interest. Methods: ELEVATE is a phase 1b/2 trial designed to evaluate the combination of elacestrant with alpelisib, everolimus, palbociclib, abemaciclib, or ribociclib. Eligible patients (pts) are women or men with ER+/HER2− locally advanced or mBC, measurable disease per RECIST v1.1 or ≥1 lytic or mainly lytic bone lesion, ECOG PS ≤1, no inflammatory breast cancer or uncontrolled central nervous system metastases, in addition to treatment-arm specific eligibility criteria as detailed below. In the phase 1b portion, pts who have received prior aromatase inhibitor (AI) and CDK4/6i will be enrolled in three 6-patient cohorts for each combination except abemaciclib (under study in a separate trial). Patients will receive elacestrant with the targeted agent at reduced or full doses. The primary endpoint of phase 1b is to determine the recommended phase 2 dose for each combination. Secondary endpoints are safety, pharmacokinetics, pharmacodynamics, and efficacy (objective response rate [ORR], duration of response [DoR], clinical benefit rate [CBR], PFS, and overall survival [OS]). The phase 2 portion will enroll 5 separate arms: A) pts with PIK3CA mutation(s) and prior AI + CDK4/6i: alpelisib + elacestrant, n=50; B) pts with prior AI + CDK4/6i: everolimus + elacestrant, n=50; C) pts with prior AI + CDK4/6i: abemaciclib or ribociclib (investigator’s [inv] choice) + elacestrant, n=60 (30 per combination); D) pts with prior AI only (no CDK4/6i): palbociclib, abemaciclib or ribociclib (inv choice) + elacestrant, n=90 (n=30 per combination); E) pts with no prior systemic therapy: palbociclib or ribociclib (inv choice) + elacestrant, n=90 (n=45 per combination). No prior fulvestrant or chemotherapy is allowed in any arm and no more than 2 prior hormonal therapies are permitted in arms A-D. Prior therapy restrictions apply to the mBC setting or within 12 months of adjuvant therapy. The primary endpoint for the phase 2 portion is the estimation of PFS at 6 months in arms A, B, and C and at 12 months in arms D and E. Secondary endpoints will include ORR, DoR, CBR, PFS, OS, and safety. The Kaplan-Meier method will be used to estimate PFS. Descriptive statistics will be used to evaluate response and safety.
Citation Format: Hope Rugo, Aditya Bardia, Javier Cortés, Giuseppe Curigliano, Erika Hamilton, Sara Hurvitz, Sibylle Loibl, Simona Scartoni, Tarek Sahmoud, Krzysztof Grzegorzewski, Nassir Habboubi, Joyce O’Shaughnessy. ELEVATE: A phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC). [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-03.