336MO - A phase II single-arm, open-label trial of pamiparib in metastatic castration-resistant prostate cancer (mCRPC) patients with deleterious germline or somatic BRCA1/2 alterations or homologous recombination deficiency (HRD): Interim analysis of efficacy and safety results

Background

Pamiparib, a poly (ADP-ribose) polymerase inhibitor (PARPi) that selectively inhibits PARP1/2, has demonstrated efficacy in several solid tumors. Homologous recombination deficiency (HRD) has been identified as an effective predictor of PARPi response in ovarian and breast cancer.

Methods

This ongoing phase II open-label study evaluates Pamiparib (40mg twice daily) in mCRPC pts with deleterious germline or somatic BRCA1/2 alterations or HRD who progressed after receiving at least one line of androgen receptor signaling inhibitors (ARSIs). BRCA alterations and HRD were detected based on paired samples of tumors and whole blood. HRD was defined as a score of ≥9, calculated from over 50,000 single-nucleotide polymorphisms (SNPs) distributed across the human genome. Preliminary data on radiologic progression-free survival (rPFS), objective response rate (ORR, based on RECIST 1.1), prostate-specific antigen (PSA) response rate (defined as a PSA decline of ≥50%), and adverse events (AEs) were reported.

Results

As of 14 Mar 2024, 25 pts were enrolled, of whom 8 carried BRCA1/2 alterations and 21 were HRD. With a median follow-up of 5.0 months (range 3.5–10.5), the rPFS was 3.5 months for all pts, 5 months for pts with BRCA1/2 mutations, and 3 months for pts with HRD. In 17 pts with evaluable targeted lesions, ORRs were 5.9%, 16.7% and 6.3% in all pts, pts with BRCA1/2 mutation and pts with HRD, respectively. PSA response rates were 25.0%, 25.0% and 27.8% in all pts, pts with BRCA1/2 mutation and pts with HRD, respectively. AEs of grade 3 occurred in 3 pts (12%) including anemia (8%) and elevated transaminase (4%). All were manageable by dose reduction/interruption. In an exploratory analysis using a threshold HRD score of 43, as established in our previous study, 5 pts were included, with a median rPFS of 7.4 months. ORR and PSA response rate was 20% and 100%, respectively.

Conclusions

The results suggest that pamiparib demonstrates significant antitumor activity as a monotherapy for mCRPC pts with deleterious germline or somatic BRCA1/2 alterations or HRD score 43.

Clinical trial identification

NCT05327621.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Beigene Ltd.

Disclosure

All authors have declared no conflicts of interest.