Elacestrant combinations in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Safety update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study.

Abstract

1079 Background: Tumors develop resistance following 1L endocrine therapy (ET) + CDK4/6i in ER+/HER2- mBC. Elacestrant (Ela) significantly improved PFS vs standard-of-care (SOC) ET ( ESR1 -mut tumors HR 0.55; 95% CI 0.39-0.77; P=0.0005; all pts HR 0.70; 95% CI 0.55-0.88; P=0.0018) with a manageable safety profile for pts with ER+/HER2- mBC and prior ET+CDK4/6i (Bidard 2022). ELEVATE (NCT05563220) evaluates Ela in combination with everolimus (Eve), alpelisib (Alp), capivasertib (Capi), ribociclib (Ribo), palbociclib (Palbo), or abemaciclib (Abema) to address different resistance mechanisms. Prior analyses have demonstrated safety consistent with the known profiles of each agent in combination with SOC ET. Ph 1b safety and efficacy evaluations reported the RP2D and antitumor activity with the following combinations: Ela + Eve (RP2D: Ela 345 mg QD + Eve 7.5 mg QD) and Ela + Abema (RP2D: Ela 345 mg QD + Abema 150 mg BID)(Ciruelos ESMO 2024, Rugo ESMO 2024). Ela 345 mg + Palbo 125 mg was determined as the RP2D (Rugo SABCS 2024). Herein, we report updated safety that includes additional pts/dose levels, and longer observation time for Ela in different combinations. Methods: Eligible pts have ER+/HER2- mBC and 1-2L of prior ET regardless of ESR1 -mut status. Objectives are to determine the RP2D (Ph 1b) and evaluate PFS (Ph 2) with each combination. Results: Table 1 reports the most common all-grade AEs from Ph 1b (Ribo, Alp, Capi combinations) and Ph 1b + Ph 2 (Eve combination) as of Dec 2024. Ela 345 mg + Ribo 400 mg QD was identified as the RP2D. Updated data will be presented. Conclusions: Elacestrant combinations continue to demonstrate safety consistent with the known profiles of each drug + SOC ET without increased risk of associated AEs. Elacestrant has the potential to become an ET backbone for multiple targeted agents, providing an all-oral treatment option in pts with ER+/HER2- mBC, delaying chemo or ADC-based regimens. Clinical trial information: NCT05563220 . Treatment-emergent AEs (≥30%). Ph 1B Ph 1B + Ph 2 Ph 1B Ph 1B Ela (86-345 mg) + Ribo (400-600 mg) (n=32) Ela (258-345 mg) + Eve (5-10 mg) (n=72) Ela (258 mg) + Alp (150-250 mg) (n=11) Ela (258-345 mg) + Capi (320 mg) (n=9) All grades, n (%) Neutropenia* 12 (38) Nausea 10 (31) Nausea 39 (54) Diarrhea 31 (43) Stomatitis 27 (38) Fatigue 23 (32) Nausea 8 (73) Vomiting 6 (55) Rash † 4 (36) Nausea 6 (67) Fatigue 5 (56) Diarrhea 5 (56) Vomiting 3 (33) Grade ≥3, n (%) Neutropenia* 8 (25) Diarrhea 5 (7) Nausea 4 (6) Fatigue 4 (6) Stomatitis 2 (3) Rash † 2 (18) Nausea 1 (9) 0 *Combined terms; † Maculopapular rash.