Abstract PS1-10-24: Compare the Data Differences between Dosing Groups in Patients with Advanced or Recurrent HR+/HER2- Breast Cancer Treated with Ecirciclib (BPI-1178) Combined with Endocrine Therapy

Abstract Background: Eciruciclib (BPI-1178) is a novel cyclin-dependent kinase (CDK) 2/4/6 inhibitor that has demonstrated potent inhibition of CDK2/4/6 expression in preclinical studies. Methods: Phase IIa had two cohorts, A and B. Cohort A included patients with HR+/HER2- advanced breast cancer (ABC) who progressed after endocrine therapy (ET) and were treated with eciruciclib and fulvestrant. In contrast, treatment-naive patients with HR+/HER2- ABC in cohort B received eciruciclib and letrozole. All patients got eciruciclib either on an intermittent (21 days on, 7 days off) or continuous (28 days on) schedule in a 28-day cycle until disease progression or unacceptable toxicity. Safety was evaluated by CTCAE 5.0. Efficacy endpoints like confirmed objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were assessed by investigators using RECIST 1.1. Results: The data released this time differs from that at ASCO 2025. As of Feb 25, 2025, cohort A enrolled 75 patients (73 evaluable for efficacy), with an ORR of 46.6% (95% CI, 34.80, 58.63), a DCR of 90.4% (95% CI, 81.24, 96.06), and a median PFS of 20.57 months. Cohort B enrolled 26 patients (25 evaluable for efficacy), with an ORR of 75.9% (95% CI, 56.46, 89.7), a DCR of 96.6% (95% CI, 82.24, 99.91), and the PFS not reached. In cohort A, the top three grade ≥ 3 TRAEs were neutrophil count decreased (38.7%), white blood cell count decreased (17.3%), and hypertriglyceridemia (14.7). In cohort B, they were neutrophil count decreased (23.3%), hypertriglyceridemia (20.0%), alanine aminotransferase increased (10.0%), and white blood cell count decreased (10.0%). Discussion: It is noteworthy that despite using the same combination drugs, there were differences in data between different dosing groups. The theoretical medication dosage per cycle was identical in both the intermittent dosing 400mg group and continuous dosing 300mg group of cohort A, both totaling 8400mg. The PFS of the continuous dosing 300mg group has not yet been reached, making comparisons currently unavailable, but its ORR is superior to the intermittent dosing 400mg group. Both groups exhibited comparable safety profiles, with no significant increase in the incidence of adverse reactions under the continuous dosing regimen. Conclusions: Under equivalent theoretical dosage, different administration regimens vary in efficacy but have comparable safety, offering valuable references for selecting the optimal dosing strategy in subsequent phases. Citation Format: Y. Du, J. Zhang, J. Wu, C. Hu, W. Chen, Y. Li, M. Yan, H. Li, W. Li, Y. Teng, T. Huang, Y. Lu, Y. Liu, D. Zhang, J. Peng, F. Gao, T. Wang, W. Zhang. Compare the Data Differences between Dosing Groups in Patients with Advanced or Recurrent HR+/HER2- Breast Cancer Treated with Ecirciclib (BPI-1178) Combined with Endocrine Therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-24.