DB-1311/BNT324 (a novel B7H3 ADC) in patients with heavily pretreated castrate-resistant prostate cancer (CRPC).

作者：Andrew Parsonson, Chintan K. Gandhi, Brian S. Henick, Andrew Schmidt, Dingwei Ye, Harshad Amin, Trisha M. Wise‐Draper, Kevin D. Courtney, Laura Tam, Shusuan Jiang, Theodore Stewart Gourdin, Aaron Lisberg, Raoul Tibes, Jenny Furlanetto, Lianghua Fang, Yang Qiu, Rong Shi, Jiawei Wei, Bin Zhang, Mark N. Stein · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.5015 · 被引用次数：7 · 研究领域：Boron Compounds in Chemistry、Radiopharmaceutical Chemistry and Applications、Prostate Cancer Treatment and Research

5015 Background: There is a high unmet need for effective therapy for patients (pts) with heavily pretreated CRPC. B7H3 ADCs have reported early clinical activity in CRPC, including DB-1311/BNT324, an investigational B7H3 ADC that received FDA Fast-Track Designation for previously treated CRPC. Methods: This phase 1/2 study (NCT05914116) enrolled pts with advanced/metastatic solid tumors, including previously treated CRPC (post docetaxel/hormonal therapy). Dose optimization cohorts randomized pts to receive 6 mg/kg or 9 mg/kg Q3W DB-1311/BNT324 until progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR, based on investigator assessment per RECIST 1.1 and PCWG3 criteria) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DOR) and radiographic progression-free survival (rPFS). Results: As of 3 Jan 2025, of 393 pts treated with DB-1311/BNT324, there were 65 pts with CRPC. Median age was 71 years (range 45–84), 49%/34%/14% were White/Asian/Black, 32%/37%/31% from Australia/USA/East Asia, 71% had ECOG PS 1, 29% had bone only disease. Median number of prior lines was 3 (range 1–14) and 28% had ≥5 prior lines. Most pts received prior docetaxel (93.8%) and hormonal therapy (96.9%); other therapies included PARP inhibitors (PARPi, 15.4%), Lutetium-177 (Lu-177, 15.4%), immunotherapy (IO, 13.8%). Among 43 response-evaluable pts (measurable disease at baseline per RECIST 1.1), best overall response was PR in...