TROP2-targeted antibody–drug conjugates (ADCs) are an emerging therapeutic approach in breast cancer. DB-1305/BNT325 is an investigational ADC that combines a humanized TROP2 monoclonal antibody with a DNA topoisomerase I inhibitor via a cleavable linker and has shown promising safety and efficacy across various tumor types. This phase 1/2 trial evaluated the efficacy and safety of DB-1305/BNT325 in patients with pretreated metastatic triple-negative breast cancer (TNBC) without prior sacituzumab govitecan treatment. In the dose-expansion part, patients received DB-1305/BNT325 until progression or unacceptable toxicity. Primary endpoints were objective response rate and safety; secondary endpoints included disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS).
As of August 31, 2025, 26 patients were enrolled and received at least 1 dose of DB-1305/BNT325 (3.5 mg/kg) every 3 weeks; 3 of 26 patients were still on treatment. The median age was 49 years (range, 29-77 years), and the majority were Asian patients (92.3%) with an ECOG performance status of 1 (65.4%). Patients received a median of 2 prior lines of therapy including chemotherapy in 100%, immunotherapy in 30.8%, and targeted therapy in 53.8% of patients.
Among 26 response-evaluable patients, at a median follow-up of 12.3 months, the confirmed ORR was 34.6% (95% confidence interval [CI], 17.21-55.67). DCR was achieved in 80.8% (95% CI, 60.65-93.45) of patients. The median PFS was 5.55 months (95% CI, 2.76-9.13). Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs reported in 34.6% of patients, including anemia (11.5%) and stomatitis (7.7%). Dose discontinuation due to TRAEs occurred in 1 patient (3.8%), while dose reductions were required in 5 patients (19.2%). No treatment-related deaths were reported. Treatment-related stomatitis led to dose reduction in 5 patients; no patients discontinued treatment due to stomatitis.
DB-1305/BNT325 demonstrated encouraging durable antitumor activity and a manageable safety profile in heavily pretreated metastatic TNBC patients. These findings support further evaluation of DB-1305/BNT325, including combination strategies with investigational agents such as BNT327, a bispecific anti–programmed death-ligand 1/VEGF-A antibody.
Source: Hamilton EP, Yan M, Wang C, et al. First clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with pretreated triple-negative breast cancer (TNBC): efficacy and safety data from a phase I/II trial. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 557P.