New TROP2-Targeted ADC Shows Promise in TNBC: Erika Hamilton,MD
Early clinical data presented on DB-1305/BNT325,a novel TROP2-targeting antibody-drug conjugate (ADC),demonstrates encouraging efficacy and a manageable safety profile in patients with pretreated,metastatic triple-negative breast cancer (TNBC). Erika Hamilton, MD, discussed the findings from a Phase 1/2 trial during a recent presentation.
The trial, open in both the United States (including Nashville, Tennessee) and China, enrolled a majority of patients from China, resulting in a predominantly Asian patient population. Dr. Hamilton acknowledged this demographic skew, noting it reflected the initial trial opening location. She also pointed out the patient population’s performance status was consistent with expectations for those with heavily pretreated, metastatic TNBC, with a prevalence of patients beyond an ECOG performance status of 0. The trial is ongoing, currently evaluating combinations with pumidimig, a PD-L/VEGF bispecific antibody, with continued enrollment in the United States.
All patients experienced treatment-related adverse events. However, Dr. Hamilton emphasized the distinct safety profiles observed across different ADCs, cautioning against generalizations. While tyrosine kinase inhibitors frequently enough present with rash and diarrhea, ADCs require individualized assessment. comparing DB-1305/BNT325 to other TROP2-targeting ADCs, she noted its side effect profile more closely resembled datopotamab deruxtecan, with stomatitis (mucosal inflammation in the mouth) being a prominent effect.
Prophylactic use of a steroid mouth rinse was recommended in the trial protocol to mitigate stomatitis, though not mandated. Dr. Hamilton highlighted challenges in accessing this preventative measure in certain regions, including China, and suggested future analysis should quantify the impact of the mouth rinse on stomatitis incidence.
A combination arm of the trial is investigating DB-1305/BNT325 with BNT327, a PD-L1/VEGF bispecific antibody. This rationale stems from emerging data supporting the synergy between ADCs and immunotherapy, especially in TNBC. While immunotherapy efficacy in TNBC and HER2-negative breast cancer isn’t fully established, trials like KEYNOTE have provided evidence supporting the benefit of combining immunotherapy with ADCs. The bispecific antibody targets both PD-L1 and VEGF, potentially boosting response rates and enabling the use of DB-1305/BNT325 in earlier lines of therapy, where immunotherapies are generally most effective.
The findings were initially presented as abstract 557P at a conference and are detailed in Ann Oncol. (2025; 36:(439). doi:10.1016/j.annonc.2025.08.980).
