Safety and efficacy of pasritamig (PAS) + docetaxel (DOCE) in participants with metastatic castration-resistant prostate cancer (mcrPc): Initial results of a phase 1b study.

Abstract

171 Background: DOCE is a standard of care for pts with mCPRC after androgen receptor pathway inhibitor (ARPI) failure, but more effective regimens are needed. PAS is a first-in-class, bispecific T-cell engaging antibody that binds to the CD3 receptor complex on T cells and to human kallikrein 2 (KLK2), which is highly and specifically expressed in prostate tissue and PC cells. PAS was well tolerated (Grade 1 cytokine release syndrome [CRS] <10%) with Q6W outpatient dosing and promising single-agent activity in a first-in-human phase 1 study in heavily pretreated mCRPC (Stein, J Clin Oncol 2025;43:2515-26). Methods: The primary objective of this open-label, Phase 1b study in mCRPC (NCT05818683) was to determine the recommended phase 2 regimen of PAS + DOCE based on safety. PAS was administered at RP2R (300 mg IV Q6W, with step-up doses of 3.5 mg on day 1 and 18 mg on day 8) in combination with DOCE (fixed dose 75 mg/m 2 IV Q3W starting on day 15) in an outpatient setting. Corticosteroids were not administered except as premedication for DOCE. Hematopoietic growth factor support was allowed. Results: As of 28 August 2025, 51 pts (median [range] age 70y [55–84], visceral metastases 33.0%) had received ≥1 dose of PAS + DOCE (median duration to date: combo, 3.5 months, PAS, 4.9 months); 31/51 pts remain on therapy (20 on combo, 11 on PAS only). Pts were heavily pretreated with a median of 3 (range 1–9) prior therapies, including ARPI (100%), DOCE (43.1%), cabazitaxel (21.6%), Lutetium-177 vipivotide tetraxetan (19.6%). PAS and DOCE were readily combinable at their full monotherapy doses with no observed dose-limiting toxicities. Treatment-related adverse events (TRAEs) were consistent with DOCE in mCRPC (Table); frequent (>20%) TRAEs included fatigue (58.8%), alopecia (41.2%), diarrhea and nausea (31.4% each), peripheral edema (25.5%), dysgeusia (21.6%). 58.8% of pts had PAS-related TRAEs. PAS TRAEs (>10%) included fatigue (29.4%) and diarrhea (11.8%). No pts had CRS of any grade. Grade ≥3 TRAEs occurred in 27.5% of pts, related serious AE in 13.7%, and TRAE leading to treatment discontinuation in 13.7% (PAS-related, n=1 each). There were no fatal TRAEs. Confirmed PSA50 was 64.7% (75.0% in taxane-naïve). Confirmed PSA90 was 35.3% (46.4% in taxane-naïve). Conclusions: PAS was readily combinable with DOCE, demonstrating a safety profile consistent with DOCE alone, no CRS, and promising anti-tumor activity in heavily pretreated patients post-ARPI/taxanes. A confirmatory phase 3 trial is planned. Clinical trial information: NCT05818683 . SAFETY Overall (N=51) PAS-related DOCE-related ≥1 TRAE, n (%) 50 (98.0) 30 (58.8) 49 (96.1) Grade ≥3 TRAE, n (%) 14 (27.5) 1 (2.0) 14 (27.5) TEAE leading to discontinuation, n (%) 7 (13.7) 1 (2.0) 7 (13.7) CRS, n (%) 0 0 0 EFFICACY Overall (N=51) Taxane-naïve pts (n=28) Confirmed PSA50, n (%) 33 (64.7) 21 (75.0) Confirmed PSA90, n (%) 18 (35.3) 13 (46.4)