A phase I/IIa study to evaluate the tolerability, safety, pharmacokinetics and efficacy of eciruciclib (BPI-1178) alone in advanced solid tumors and in combination with endocrine therapy for advanced or recurrent HR+/HER2- breast cancer.

Abstract

1064 Background: Eciruciclib (BPI-1178) is a new cyclin-dependent kinases (CDKs) 2/4/6 inhibitor, which has shown strong inhibition on the expression of CDK2/4/6 in pre-clinical studies. This first-in-human phase I/IIa study aimed to assess the preliminary efficacy, safety and tolerability of eciruciclib monotherapy for advanced solid tumors or in combination with endocrine therapy (ET) for HR+/HER2- advanced breast cancer (ABC). Methods: Patients with advanced solid tumors included in phase I received eciruciclib alone at doses of 25~500 mg in a 3+3 dose-escalation or expansion manner. Phase IIa consisted of two cohorts, A and B. Cohort A included patients with HR+/HER2- ABC who had progressed after ET receiving eciruciclib in combination with fulvestrant, and treatment-naive patients with HR+/HER2- ABC in cohort B were treated with eciruciclib in combination with letrozole. All patients administered eciruciclib with either intermittent (21 days on, 7 days off) or continuous (28 days on) dosing schedule in a 28-day cycle until disease progression, unacceptable toxicity, etc. Safety was assessed as per CTCAE 5.0. Efficacy endpoints included confirmed objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), etc. assessed by investigators per RECIST 1.1. Results: As of August 9, 2024, a total of 129 patients have been enrolled. And 33 patients were enrolled in Phase l study. No DLT was observed. In Phase IIa Cohort A, 70 patients were enrolled and in which 64 patients were evaluable for efficacy. 26 patients were enrolled into cohort B with 25 efficacy-evaluable patients. In Cohort A, the top three treatment related adverse events (TRAEs) of grade ≥ 3 were neutrophil count decreased (35.7%), white blood cell count decreased (14.3%), and hypertriglyceridemia (14.3%) while in Cohort B those were neutrophil count decreased (23.3%), hypertriglyceridemia (16.7%), alanine aminotransferase increased (10.0%), and white blood cell count decreased (10.0%). No TRAE leading to permanent discontinuation or death occurred in this trial. Conclusions: Eciruciclib in combination with ET demonstrated promising efficacy and manageable safety profile in patients with HR+/HER2- ABC. Clinical trial information: NCT04282031 . Cohort A (n = 64) Cohort B (n = 25) 400 mg a 300 mg a 300 mg b 200 mg b 400 mg a 300 mg a (n = 20) (n = 16) (n = 20) (n = 8) (n = 19) (n = 6) ORR, n (%) 9 (45.0) 7 (43.8) 11 (55.0) 0 15 (78.9) 5 (83.3) DCR, n (%) 17 (85.0) 13 (81.3) 20 (100.0) 8 (100.0) 18 (94.7) 6 (100.0) Median PFS, 18.3 7.3 NR NR NR NR months (95% CI) (7.2, NR) (2.4, NR) (12.8, NR) (16.7, NR) a intermittent dosing schedule; b continuous dosing schedule; NR, not reached.