DB-1311/BNT324 (a novel B7H3 ADC) in patients with heavily pretreated mCRPC from a phase 1/2 study: Analyses according to prior treatment with lutetium 177 (177Lu)-PSMA-617.
Year: 2026
Type: conference-abstract
Abstract: 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
Source: Journal of Clinical Oncology
Authors: Mark N. Stein, Andrew Ohyama Parsonson, Theodore Stewart Gourdin, Brian S. Henick, Kevin Dale Courtney, Chintan Gandhi, Robert Allison Franklin, Trisha Michel Wise-Draper, Andrew L Schmidt, Harshad Amin, Laura Tam, HongQian Guo, Shusuan Jiang, Xuesong Li, Wei Yu, Aaron Lisberg, Raoul Tibes, Hua Mu, Jiawei Wei, Dingwei Ye
Institutions: Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, Macquarie University, Medical University of South Carolina, MUSC Hollings Cancer Center, Columbia University, The University of Texas Southwestern Medical Center, BRCR Global (United States), University of Cincinnati Medical Center, University of Cincinnati, Sunshine Coast University Hospital, Queensland Health, Nanjing Drum Tower Hospital, Hunan Cancer Hospital, Peking University First Hospital, University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center, BioNTech (Germany), Duality Biotherapeutics, Inc. (China), Fudan University Shanghai Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7133200541