Background: Androgen receptor (AR) signaling inhibition increases genomic instability of double-stranded DNA breaks, and co-inhibition of AR and PARP induces synthetic lethality in multiple preclinical models. In this study we tested the efficacy and safety of neoadjuvant pamiparib plus abiraterone and ADT in HRLPC/VHRLPC before radical prostatectomy (RP). Methods: In this phase II single-arm neoadjuvant trial, patients with HRLPC/VHRLPC (defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA≥ 20 ng/mL) were enrolled to evaluate the safety and antitumor efficacy of pamiparib before prostatectomy. Patients received pamiparib plus abiraterone and ADT for 4 months followed by prostatectomy. The primary objective was the rate of pathological complete response (pCR) or minimal residual disease (MRD). MRD was defined as ≤0.5cm of tumor or residual cancer burden ≤0.25 cm3 (RCB = tumor volume x cellularity). Secondary endpoints include PSA response, surgical staging at RP, the rate of PSA recurrence 12 months after surgery, and safety. Results: A total of 30 pts were enrolled, 29 pts (HRRm n=7) completed the full course of study treatment and underwent RP. One patient declined surgery for personal reasons and received further systemic therapy. The median age was 66 (range 41-77). Clinical characteristics were typical of high-risk disease: median PSA 34.4 ng/ml (range 10.8-204) and clinical stage cT3 (n=27), Gleason 8-10 (n=20),9 pts had enlarged pelvic lymph nodes. Following 4 months of therapy, the median pre-RP PSA was 0.103 ng/ml (range 0.006 -1.1). Final pathologic results showed that 8 pts (27.5%) achieved pCR or MRD, 3 pts (10.3%) achieved pCR, 5 patients (17.2%) achieved MRD, and 18 patients (62%) had staging downgrades, with no patients experiencing progression. Compared to patients with an HRR wild type (HRRwt), those with HRR mutations had no difference in pCR or MRD. The margin positivity rate was 6.8%(n=2) in 29 pts, all of whom were T3 stage patients. No Grade 3/4 drug-related adverse event was observed. The most common 1-2 adverse event were anaemia (48.2%), AST/ALT increased (34.4%) and hypertriglyceridemia (44.8%). Conclusions: Neoadjuvant therapy of pamiparib plus abiraterone and ADT for 4 months was effective and safe in pts with HRLPC/VHRLPC. Clinical trial information: NCT05376722.