Abstract PS5-02-29: Clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with metastatic triple negative breast cancer (mTNBC): Efficacy and safety data from a phase 1/2 trial

Abstract Background DB-1305/BNT325 is a novel investigational ADC with a humanized TROP2 IgG1 monoclonal antibody linked to a DNA topoisomerase I inhibitor via a cleavable linker. Early clinical data showed a manageable safety profile and encouraging activity across tumor types, particularly in ovarian cancer (Marathe, ESMO 2023 & Rubinstein, SGO 2025). This study evaluated DB-1305/BNT325 in pts with previously treated mTNBC. Methods In the dose expansion part of this Phase 1/2 trial, pts with mTNBC (w/o prior sacituzumab govitecan) received DB-1305/BNT325. The primary endpoints were objective response rate (ORR), based on investigator assessment per RECIST 1.1, and safety. Secondary endpoints included disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS). Results As of March 31, 2025, 26 pts with TNBC had received ≥1 dose of DB-1305/BNT325, with 6 pts still on treatment. The cohort is fully enrolled. Median age was 49 years (range: 29-77); most pts were Asian (92.3%) and had ECOG PS 1 (65.4%). Most common metastases sites were bone (50%), lung (38.5%), and liver (34.6%). The median number of prior lines of treatment was 2 (range: 2-6), including immunotherapy in 8 (30.8%), platinum-based chemotherapy in 19 (73.1%), and bevacizumab in 5 (19.2%) pts. Efficacy data (summarized in the table) is available for all 26 pts after a median follow-up of 9.3 months. Treatment-emergent and treatment-related adverse events (TRAEs) occurred in all 26 pts, with Grade ≥3 in 9 (34.6%) pts. TRAEs led to dose reduction in 5 pts (19.2%) and discontinuation in 1 pt (3.8%, due to anemia). No TRAEs resulted in death. The most common TRAEs were stomatitis (any grade: 69.2%, Grade ≥3: 7.7%), anemia (any grade: 53.8%, Grade ≥3: 11.5%), nausea (any grade 46.2%, Grade ≥3: 0%), decreased neutrophil (any grade: 46.2%, Grade ≥3: 0%) and white blood (any grade: 46.2%, Grade ≥3: 3.8%) cell count. Updated analyses from the cohort will be presented. Conclusions The data suggest an encouraging efficacy and manageable safety profile of DB-1305/BNT325 in pts with pretreated TNBC, with only 1 patient discontinuing treatment due to TRAE. DB1305/BNT325 is now being evaluated in combination with BNT327, an investigational anti-PD-L1 x VEGF-A bispecific antibody in pts with TNBC. Citation Format: E. Hamilton, D. A. Aysel, M. Yan, C. Wang, H. Yang, J. Shi, W. Xie, H. Wang, Y. Sun, X. Sun, B. Zhang, Q. Yang, Z. Jia, H. Mu, S. Tillmanns, Y. Barbachano, J. Furlanetto, T. Sun. Clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with metastatic triple negative breast cancer (mTNBC): Efficacy and safety data from a phase 1/2 trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-02-29.