Imlunestrant in ER-Positive Advanced Breast Cancer and Endometrial Endometrioid Cancer: EMBER Results

Imlunestrant dose-escalation studies exhibited encouraging safety, pharmacokinetics (PK), and preliminary efficacy in patients with ER-positive/HER2-negative advanced breast cancer, and ER-positive endometrial endometrioid cancer.

Patients with ER-positive advanced breast cancer and ER-positive endometrial endometrioid cancer were enrolled in EMBER. Patients with ER-positive advanced breast cancer included those with previous endocrine therapy (ET) sensitivity and ≤3 previous treatments for advanced breast cancer in phase 1a following protocol changes and ≤2 in phase 1b. Patients with ER-positive endometrial endometrioid cancer included those who had received previous platinum therapy but no previous fulvestrant or aromatase inhibitors. Premenopausal women were given a gonadotropin-releasing hormone agonist at the same time. Serial plasma samples were taken for PK and circulating tumor DNA analysis. Critical end points were comprised of recommended phase 2 dose (RP2D) determination, safety and tolerability, PK, objective overall response rate (ORR), complete response (CR), or partial response (PR) per RECIST version 1.1 in patients with measurable disease and ≥1 post-baseline tumor assessments or discontinued previous to tumor assessment, and clinical benefit rate (CBR), CR or PR, or stable disease lasting ≥24 weeks in patients enrolled ≥24 weeks prior to data cutoff.

Imlunestrant monotherapy was given to 138 patients (n = 114 advanced breast cancer, n = 24 endometrial endometrioid cancer) as of January 14, 2022, at doses ranging from 200 mg to 1200 mg daily. The median age was 62.0 years (range, 32-95 years). The median number of previous therapies for advanced breast cancer was 2 (range, 0-8); for endometrial endometrioid cancer, it was 1 (range, 0-5). Patients with advanced breast cancer had previously had ET (94.7%), cyclin-dependent kinase (CDK)4/6 inhibitor therapy (92.1%), fulvestrant (50.9%), and chemotherapy (26.3%).

No dose-limiting toxicities were found. Most treatment-emergent adverse events (TEAEs) were grade 1. The most common all-grade TEAEs at the RP2D (400 mg daily, n = 69) were nausea (33.3%), fatigue (27.5%), and diarrhea (23.2%). The rate of grade 3 TEAEs across all dosages was 3.6%. No patients ceased medication as a result of a TEAE. ORR was 8.0% (6 of 75 patients) and CBR was 40.4% (42 of 104 patients) in evaluable patients with advanced breast cancer. ORR was 5.0% (1 of 20 patients had a PR pending confirmation), and CBR was 47.1% (8 of 17 patients) in evaluable patients with endometrial endometrioid cancer. Clinical benefit was observed regardless of the baseline ESR1 mutation status.

In conclusion, imlunestrant continues to show an overall favorable safety profile, with no cardiac or ophthalmic issues, and continues to show antitumor activity following treatment with a CDK4/6 inhibitor, demonstrating evidence of clinical activity mainly due to disease stabilization in pretreated patients with ER-positive advanced breast cancer and endometrial endometrioid cancer.

Source

Komal L, Jhaveri KL, Jeselsohn R, et al. 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. J Clin Oncol. 2022;40:16. Abstract 1021.