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 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)
Patel et al. (2026) studied this question.