Abstract CT027: Imlunestrant, a novel orally bioavailable selective estrogen receptor degrader (SERD) in Chinese patients with ER positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer (

Abstract Background: Imlunestrant is a novel, orally bioavailable SERD under development for breast cancer treatment. In preclinical studies, it shows strong activity against both wild-type and mutant estrogen receptors, effectively inhibiting tumor growth. Oral administration with a favorable safety profile makes it convenient to use. Methods: Chinese patients with ER+/HER2- locally advanced or mBC were randomized in a 1:1 ratio to receive oral imlunestrant 400 mg or 200 mg once daily until disease progression or unacceptable toxicity (NCT05509790). PK, safety and efficacy of imlunestrant were assessed. Results: A total of 17 patients were randomized to imlunestrant 400 mg (N=9) or 200 mg (N=8). All enrolled patients were female with a median age of 57.0 years (range: 43-79). All had mBC and received prior systemic anti-cancer therapies for advanced disease, of which 12 patients received three or more regimens. As of the data cut-off date (18 FEB 2024), 2 patients in each dosing cohort remained on treatment. Maximum plasma concentrations of imlunestrant were reached approximately 4 hours after a single oral dose. The mean half-life (t1/2) was approximately 20 to 22 hours. The accumulation ratio was approximately 2.3-fold. Imlunestrant was well tolerated with the majority of treatment-emergent adverse events (TEAEs) being Grade 1 or 2. The most common TEAEs (reported by ≥ 2 patients) in the imlunestrant 400 mg cohort were leukopenia, neutropenia, anemia, diarrhea, influenza-like disease, COVID-19, and hypertriglyceridemia. The most common TEAEs in the imlunestrant 200 mg cohort were anemia, AST increased, gamma-glutamyltransferase increased, hypercholesterolemia, ALT increased, blood lactate dehydrogenase increased, hyperbilirubinemia, thrombocytopenia, and upper respiratory tract infection. No clinically significant changes of lab values were identified. One patient in the imlunestrant 400 mg cohort had a Grade 4 serious adverse event of neutrophil count decrease, which was not related to study treatment. No patients discontinued or died due to adverse events (AEs). As of data cut-off date, the median duration of treatment was 8.3 weeks (range: 2.7-44.6). The ORRs in the imlunestrant 400 mg and 200 mg cohorts were 11.1% (1/9) and 12.5% (1/8); the DCRs were 33.3% (3/9) and 50.0% (4/8), respectively. The PFS rates at 6 months in the imlunestrant 400 mg and 200 mg cohorts were 37.5% and 42.9%, respectively. Conclusion: The PK parameters of oral imlunestrant in Chinese patients were comparable to those observed in global populations. Imlunestrant monotherapy was well tolerated, with no new safety signals identified and demonstrated preliminary anti-tumor activity in Chinese patients. Citation Format: Jian Zhang, Yiping Zhu, Hui Liang, Wenyan Chen, Shenqi Wang, Liu Yang, Eunice Yuen, Xuemei Zhang, Jiawei Xu. Imlunestrant, a novel orally bioavailable selective estrogen receptor degrader (SERD) in Chinese patients with ER positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer (mBC): Results from a phase 1 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT027.