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Background <p>Studies have shown that poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors can potentiate the antitumor effect of abiraterone acetate plus prednisone (AA-P) in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the pharmacokinetics, safety, and efficacy of fuzuloparib, a PARP inhibitor, in combination with AA-P in mCRPC patients who had not received prior novel hormonal agents.</p> Methods <p>This was a dose escalation and expansion study. In dose escalation, eligible patients received fuzuloparib at 100 or 150&#xa0;mg BID for 5 days, followed by fuzuloparib plus AA-P (abiraterone acetate 1000&#xa0;mg QD, prednisone 5&#xa0;mg BID) in 28-day treatment cycles. The higher tolerated dose of fuzuloparib was selected for dose expansion. In dose expansion, two treatment groups were planned. The fuzuloparib group received fuzuloparib for 5 days, and the abiraterone group received AA-P for 5 days. Both groups were then treated with the combination therapy.</p> Results <p>A total of 39 patients were enrolled and treated. As of July 12, 2023, the median follow-up time was 23.2 months (range, 3.9−44.3). No obvious drug-drug interaction was observed between 150&#xa0;mg fuzuloparib and AA-P, and no dose-limiting toxicities were identified. Treatment-related adverse events (TRAEs) occurred in 36 (92.3%) patients, of which 20 (51.3%) reported grade ≥ 3 TRAEs. At the end of Week 12, prostate-specific antigen (PSA) response rate was 71.8% (95% CI, 55.1−85.0). The median time to PSA progression was 19.4 months (95% CI, 11.3−27.8). Objective response rate was 60% and disease control rate was 90% among patients with evaluable target lesions. The median duration of response was 8.1 months (95% CI, 4.6−31.5), and the median time to radiographic progression was 27.9 months (95% CI, 14.0−not reached). Time to disease progression was generally longer in patients with homologous recombination repair gene mutations, including those with <i>BRCA</i> mutations.</p> Conclusions <p>Fuzuloparib plus AA-P had an acceptable safety profile and showed promising efficacy among mCRPC patients.</p> Trial registration <p>ClinicalTrials.gov, NCT04108247 (Registered on September 26, 2019).</p>

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Pharmacokinetics, safety, and efficacy of fuzuloparib in combination with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer: a phase 1 dose escalation and expansion study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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  • Tao Dai,
  • Zhenzhou Xu,
  • Haitao Wang,
  • Weiqing Han,
  • Dahong Zhang,
  • Kaifa Tang,
  • Xinshuai Wang,
  • Jian Huang,
  • Chaohong He,
  • Xianfeng Zhou,
  • Dapeng Zhang,
  • Chun Yang

摘要

Background

Studies have shown that poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors can potentiate the antitumor effect of abiraterone acetate plus prednisone (AA-P) in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the pharmacokinetics, safety, and efficacy of fuzuloparib, a PARP inhibitor, in combination with AA-P in mCRPC patients who had not received prior novel hormonal agents.

Methods

This was a dose escalation and expansion study. In dose escalation, eligible patients received fuzuloparib at 100 or 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. The higher tolerated dose of fuzuloparib was selected for dose expansion. In dose expansion, two treatment groups were planned. The fuzuloparib group received fuzuloparib for 5 days, and the abiraterone group received AA-P for 5 days. Both groups were then treated with the combination therapy.

Results

A total of 39 patients were enrolled and treated. As of July 12, 2023, the median follow-up time was 23.2 months (range, 3.9−44.3). No obvious drug-drug interaction was observed between 150 mg fuzuloparib and AA-P, and no dose-limiting toxicities were identified. Treatment-related adverse events (TRAEs) occurred in 36 (92.3%) patients, of which 20 (51.3%) reported grade ≥ 3 TRAEs. At the end of Week 12, prostate-specific antigen (PSA) response rate was 71.8% (95% CI, 55.1−85.0). The median time to PSA progression was 19.4 months (95% CI, 11.3−27.8). Objective response rate was 60% and disease control rate was 90% among patients with evaluable target lesions. The median duration of response was 8.1 months (95% CI, 4.6−31.5), and the median time to radiographic progression was 27.9 months (95% CI, 14.0−not reached). Time to disease progression was generally longer in patients with homologous recombination repair gene mutations, including those with BRCA mutations.

Conclusions

Fuzuloparib plus AA-P had an acceptable safety profile and showed promising efficacy among mCRPC patients.

Trial registration

ClinicalTrials.gov, NCT04108247 (Registered on September 26, 2019).