1650P - Fuzuloparib plus abiraterone acetate and prednisone (AA-P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase I study

Background

AA-P is currently the first-line and second-line treatment in pts with mCRPC. PARP inhibitors plus AA-P has the potential to enhance the anti-tumour activity of abiraterone. In this study, we aimed to evaluate the PARP inhibitor fuzuloparib in combination with AA-P in mCRPC pts.

Methods

This was a 3+3 dose escalation and expansion study in mCRPC pts who had not received prior novel hormonal agents. Eligible pts received fuzuloparib (at escalating doses of 100 and 150 mg BID) for 5 days, followed by fuzuloparib plus AA-P (abiraterone acetate 1000 mg QD, prednisone 5 mg BID) in 28-day treatment cycles. Dose limiting toxicities (DLTs) were observed during the monotherapy and first treatment cycle. Dose expansion started with Group A receiving fuzuloparib at the higher tolerated dose for 5 days and Group B receiving AA-P for 5 days, followed by combination therapies in both groups. Primary objectives were pharmacokinetics and safety.

Results

As of July 20, 2023, 39 pts were enrolled (median follow-up time, 23.2 mo [range, 3.9-44.3]), including 3 in the fuzuloparib 100 mg cohort and 36 in the fuzuloparib 150 mg cohort. No obvious drug-drug interaction was observed with fuzuloparib at 150 mg (n = 36). The combination therapy did not affect exposure (C_max and AUC_ss) to abiraterone and had limited effect on exposure to fuzuloparib. There were no DLTs identified. Treatment-related adverse events (TRAEs) occurred in 36 (92.3%) pts, of which 20 (51.3%) reported grade >=3 TRAEs. The most common TRAEs were anaemia (53.8%; grade >=3, 17.9%) and decreased weight (25.6%; grade >=3, 2.6%). There were no unexpected TRAEs or TRAEs leading to death. At Week 12, 28 (71.8%) pts had >=50% reduction in prostate-specific antigen (PSA) from baseline. The maximum reduction in PSA exceeded 50% for 31 (79.5%) pts and 90% for 24 (61.5%) pts. ORR was 60% in pts with measurable lesions. Median PSA PFS was 19.4 mo (95% CI, 11.27-22.76), median rPFS was 27.9 mo (95% CI, 14.0-not reached [NR]), and median DoR was 31.5 mo (95% CI, 4.57-NR) among all pts.

Conclusions

Fuzuloparib plus AA-P had limited drug-drug interaction. The combination therapy was generally tolerated with acceptable safety profile and showed promising efficacy among mCRPC pts.

Clinical trial identification

NCT04108247.

Editorial acknowledgement

Medical writing support was provided by Xinyu Xie (Jiangsu Hengrui Pharmaceuticals).

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

X. Zhou, D. Zhang, C. Yang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.