176 Background: 177Lu-PSMA-617 (Lu 177) has reported improved outcomes in metastatic hormone sensitive and castration resistant prostate cancer (mHSPC/mCRPC); however, there is still a high unmet need, particularly for patients (pts) with mCRPC. Moreover, data on clinical outcomes following Lu 177 is limited. DB-1311/BNT324 is an investigational B7H3 ADC with encouraging activity in pts with heavily pretreated mCRPC (ASCO 2025 #5015). Herein we present new clinical results with a focus on pts with mCRPC who received Lu 177 treatment. Methods: In the dose optimization cohort of this phase 1/2 study (NCT05914116), pts with previously treated mCRPC received DB-1311/BNT324 6 mg/kg or 9 mg/kg Q3W, while in the dose expansion cohorts (post Lu 177 mCRPC and taxane-naïve mCRPC), pts received 6 mg/kg Q3W until progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR, using PCWG3-modified RECIST v1.1) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DOR), radiographic progression-free survival (rPFS), overall survival (OS), PSA response and PSA DOR. Results: At data cut-off (05 Sept, 2025) 104 pts with mCRPC had been treated (6 mg/kg n=68; 9 mg/kg n=34) with 52 pts (50%) still on treatment after a median follow-up of 9.2 mos (range 0.1–19.4). Median age was 70 yrs (range 45–90); 71% enrolled in US/AUS, 29% in China; 53% were White, 31% Asian, 13% Black; median prior lines was 4 (range 1–14). Among 58 response-evaluable pts (measurable disease at baseline per RECIST 1.1), unconfirmed ORR was 41.4% (95% CI 28.6, 55.1), confirmed ORR (cORR) was 34.5%, and DCR was 87.9% (95% CI 76.7, 95.0). Median DOR was 10.2 mos (95% CI 7.2, ne). Median rPFS (N=82) was 11.3 mos (95% CI 7.2, ne) with 6-mo rPFS rate of 72.0% and 9-mo rPFS rate of 63.0%. OS was immature at data cut-off, but encouraging 6-mo (91.7%) and 9-mo OS (88.2%) rates were observed. PSA 50 response rate was 35.4% and median PSA DOR was 8.4 mos (95% CI 4.4, NE). Safety data were in line with previous report at ASCO 2025, with nausea and hematological events, primarily Grade 1–2, being most common. Thirty-four (33%) pts received prior Lu 177 (median age: 69 yrs range 55–84; 65% White, 15% Asian, 15% Black; median prior lines: 5 range 2–14) with 24 (71%) still on treatment. Outcomes were similar in pts who received prior Lu 177 and pts who did not (Table). Conclusions: DB-1311/BNT324 showed encouraging durable efficacy in heavily pretreated mCRPC including patients who were previously treated with 177Lu-PSMA-617 with no new safety signals reported. Further development of DB-1311/BNT324 in mCRPC is warranted. Clinical trial information: NCT05914116 . Post Lu 177 No prior Lu 177 Response evaluable, n 10 48 cORR, % 30.0 35.4 DCR, % 100 85.4 Efficacy evaluable, n 23 59 Median rPFS, months 11.3 NE 9-month rPFS rate, % 61.1 63.7 9-month OS rate, % 86.2 88.5 PSA 50 response rate, % 30.4 37.3
Stein et al. (2026) studied this question.