Abstract PS15-09: Imlunestrant monotherapy and in combination with abemaciclib, with or without an aromatase inhibitor, in estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC): updated results from the EMBER study
Authors: Jhaveri Komal , Lim Elgene , Jeselsohn Rinath , Ma Cynthia , Hamilton Erika , Osborne Cynthia , Bhave Manali , Kaufman Peter , Beck J. Thaddeus , Manso Luis , Parajuli Ritesh , Wang Hwei-Chung , Tao Jessica , Dhakal Ajay , Pierga Jean-Yves , Lu Yen-Shen , Larson Tim , Gilarranz Yolanda Jerez , Ismail-Khan Roohi , Bacchion Francesca , Karacsonyi Claudia , Li Yujia , Estrem Shawn T. , Nguyen Bastien , Beeram Muralidhar 
Published: May 2024

Abstract
Background:
Imlunestrant is an oral, brain-penetrant selective estrogen receptor degrader, designed to deliver continuous ER target inhibition, including in ESR1-mutant breast cancer. In the first-in-human dose escalation/expansion (Phase 1a/1b) study of the EMBER trial (NCT04188548), imlunestrant showed favorable safety, pharmacokinetics, and clinical benefit in pre-treated patients with ER+, HER2- aBC when administered as monotherapy (Jhaveri, ASCO 2022) or with abemaciclib ± aromatase inhibitor (AI) (Jhaveri, SABCS 2022). Here, we report updated data from Phase 1a/1b of imlunestrant monotherapy as well as from Phase 1b of imlunestrant with abemaciclib ± AI in EMBER.
Methods:
Phase 1a/1b enrolled patients with ER+ aBC (prior endocrine therapy (ET) sensitivity or untreated de novo aBC). Prior aBC therapy allowance was ≤3 (no restrictions on the type of prior therapies) in Phase 1a and ≤2 (only 1 prior ET) in Phase 1b for patients receiving imlunestrant monotherapy; and ≤1 (no prior CDK4/6 inhibitors) in Phase 1b for patients randomized to receive imlunestrant + abemaciclib ± AI. Key endpoints included safety and tolerability, objective response rate (ORR: complete response (CR) or partial response (PR) in patients with measurable disease), clinical benefit rate (CBR: CR or PR, or stable disease ≥24 weeks) per RECIST v1.1, and progression-free survival (PFS).
Results:
As of March 2023, 114 patients received imlunestrant monotherapy (200mg n=21; 400mg (RP2D) n= 51; ≥600mg n=42), and 85 patients received imlunestrant (400mg n=80; 800 mg n=5) in combination with abemaciclib ± AI (both at labeled doses). At the RP2D, the most common all-grade/Grade 3 treatment-emergent adverse events (TEAEs) with imlunestrant monotherapy were fatigue (39%/4%), nausea (39%/2%), and diarrhea (29%/2%). With the combination of imlunestrant + abemaciclib ± AI, the most common all-grade/Grade 3 TEAEs were diarrhea (88%/9%), nausea (61%/0%), fatigue (51%/5%), and neutropenia (44%/16%). No safety signals of ocular or cardiac toxicity (bradycardia/QTc prolongation) were observed. Baseline characteristics, safety, and preliminary efficacy are presented in Table 1. Combination therapy of imlunestrant and abemaciclib ± AI improved ORR and CBR.
Conclusion:
With longer follow-up, imlunestrant alone or in combination with abemaciclib ± AI continues to demonstrate a tolerable safety profile along with favorable preliminary efficacy in patients with ER+, HER2- aBC. Further data will be presented at the meeting. The Phase 3, EMBER-3 study is ongoing; evaluating imlunestrant, investigator’s choice ET, and imlunestrant plus abemaciclib in ET pre-treated ER+, HER2- aBC patients (NCT04975308).
Table. Baseline characteristics, safety and preliminary efficacy a, in patients with available ctDNA data.
Citation Format: Komal Jhaveri, Elgene Lim, Rinath Jeselsohn, Cynthia Ma, Erika Hamilton, Cynthia Osborne, Manali Bhave, Peter Kaufman, J. Thaddeus Beck, Luis Manso, Ritesh Parajuli, Hwei-Chung Wang, Jessica Tao, Ajay Dhakal, Jean-Yves Pierga, Yen-Shen Lu, Tim Larson, Yolanda Jerez Gilarranz, Roohi Ismail-Khan, Francesca Bacchion, Claudia Karacsonyi, Yujia Li, Shawn T. Estrem, Bastien Nguyen, Muralidhar Beeram. Imlunestrant monotherapy and in combination with abemaciclib, with or without an aromatase inhibitor, in estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC): updated results from the EMBER study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-09.