A phase 1a/b trial of imlunestrant (LY3484356), an oral selective estrogen receptor degrader (SERD) in ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Monotherapy results from EMBER.

• DOI: 10.1200/jco.2022.40.16_suppl.1021
• Publication Date: 2022-06-06T15:53:25Z
• Authors: Komal L. Jhaveri; Rinath Jeselsohn; Elgene Lim; Erika P. Hamilton; Kan Yonemori; J. Thaddeus Beck; Peter A. Kaufman; Sarah Sammons; Manali A. Bhave; Cristina Saura; Emiliano Calvo; Tarek Meniawy; Timothy Larson; Cynthia X. Ma; Javier García-Cor...; Shanshan Cao; Shawn T. Estrem; Jennifer L. Milata; Bastien Nguyen; Muralidhar Beeram
• Keywords: Fulvestrant; Tolerability; Concomitant; Aromatase inhibitor

1021 Background: Imlunestrant is a novel, orally bioavailable SERD with pure antagonistic properties that result in sustained inhibition of ER-dependent gene transcription and cell growth. In dose escalation, imlunestrant showed favorable safety, pharmacokinetics (PK) preliminary efficacy patients ER+, HER2- aBC ER+ EEC (Phase 1a EMBER, Jhaveri 2021). Here we present updated data from the escalation 1a) expansion 1b) monotherapy EMBER (NCT04188548). Methods: Phase 1a/1b enrolled (prior ET sensitivity; ≤3 prior therapies for following protocol amendment ≤2 platinum therapy; no fulvestrant or aromatase inhibitor). Premenopausal women received concomitant GnRH agonist. Serial plasma samples were obtained PK ctDNA analysis. Key endpoints included recommended phase 2 (RP2D) determination, safety tolerability, PK, objective response rate per RECIST v1.1 (ORR: complete [CR] partial [PR]) measurable disease ≥1 post-baseline tumor assessment discontinued to assessment, clinical benefit (CBR: CR PR, stable ≥24 weeks) weeks cut. Results: As January 14, 2022, 138 (n = 114 aBC, n 24 EEC) at doses ranging 200-1200 mg QD. Median age was 62.0 years (range 32-95). number 0-8) 1 (0-5), respectively. had (94.7%), CDK4/6 inhibitor (92.1%), (50.9%) chemotherapy (26.3%). No dose-limiting toxicities observed. Most treatment-emergent adverse events (TEAEs) grade 1. At RP2D (400 QD, n= 69), most common all TEAE’s nausea (33.3%), fatigue (27.5%), diarrhea (23.2%). Across doses, incidence treatment-related 3 AEs low (3.6%). patient due TEAE. evaluable patients, ORR 8.0% (6/75) CBR 40.4% (42/104). 5.0% (1/20 PR- ongoing pending confirmation) 47.1% (8/17). Clinical observed regardless baseline ESR1 mutation status as determined by sequencing. Additional biomarker analyses will be presented meeting. Conclusions: continues demonstrate side effect profile, cardiac opthalmic signals, has continued evidence activity heavily pre-treated patients. trial information: NCT04188548.