55 TIP ELEVATE: A Phase 1b/2, Open-Label, Umbrella Study Evaluating Elacestrant in Various Combinations in Women and Men With Metastatic Breast Cancer (mBC)

Background

Elacestrant demonstrated significantly prolonged PFS, and had a manageable safety profile compared with standard of care endocrine therapy in the phase 3 EMERALD trial that enrolled patients (pts) with ER+/HER2− mBC following disease progression on prior endocrine and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy. The benefit was observed in the overall population and in pts with ESR1 mutations. Combining elacestrant with targeted agents utilized in combination with endocrine therapy in mBC is of therapeutic interest.

Materials and Methods

ELEVATE is a phase 1b/2 trial designed to evaluate elacestrant combined with alpelisib, everolimus, palbociclib, abemaciclib, or ribociclib. Eligible pts are women/men with ER+/HER2− locally advanced or mBC, measurable disease per RECIST v1.1 or ≥1 lytic/mainly lytic bone lesion, ECOG PS ≤1, no inflammatory BC or uncontrolled CNS metastases, plus treatment-arm specific eligibility criteria as detailed below. In the phase 1b portion, pts who 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). Pts will receive elacestrant + targeted agent at reduced or full doses. The primary end point of phase 1b is to determine the RP2D for each combination. Secondary end points are safety, PK, PD, and efficacy (ORR, DoR, CBR, PFS, and 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 ≤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 phase 2 primary end point is the estimation of PFS at 6 months in arms A, B, and C and at 12 months in arms D and E. Secondary end points include ORR, DoR, CBR, PFS, OS, and safety.

Status

Recruitment for ELEVATE began in January 2023.

AFFILIATIONS:

Hope S. Rugo,¹ Aditya Bardia,² Javier Cortes,³ Giuseppe Curigliano,^4,5 Erika Hamilton,⁶ Sara Hurvitz,⁷ Sibylle Loibl,⁸ Simona Scartoni,⁹ Tarek Sahmoud,¹⁰ Krzysztof J. Grzegorzewski,¹⁰ Nassir Habboubi,¹⁰ Joyce O’Shaughnessy¹¹

¹University of California San Francisco Comprehensive Cancer Center, San Francisco, CA.

²Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.

³International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain.

⁴European Institute of Oncology IRCCS, Milan, Italy.

⁵University of Milano, Milan, Italy.

⁶Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN.

⁷UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA.

⁸German Breast Group, Neu-Isenburg, Germany; Centre for Haematology and Oncology Bethanien, Frankfurt, Germany.

⁹Menarini Group, Florence, Italy.

¹⁰Stemline Therapeutics/Menarini Group, New York, NY.

¹¹Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX.