Evolving ADC Strategies in TNBC: From Chemotherapy Replacement to Novel Targets

Recent trials, including ASCENT-04 and TROPION-BREAST03, are reshaping the role of antibody–drug conjugates (ADCs) in triple-negative breast cancer (TNBC), particularly in combination with immunotherapy. Data suggest that ADCs may effectively replace chemotherapy in these regimens, offering comparable efficacy with a more favorable safety profile, including reduced hematologic and gastrointestinal toxicity. Clinically, this shift could enhance patient tolerability, maintain dose intensity, and expand options for those ineligible for traditional chemotherapy. Beyond established ADCs, novel targets and payloads are under active investigation. Agents such as Emiltatug ledadotin, XMT-1660 (B7-H4-directed Dolasynthen ADC), and enfortumab vedotin (Nectin-4-directed) demonstrate promising preclinical and early clinical activity, highlighting the potential to address resistance mechanisms and tumor heterogeneity. These advancements underscore a rapidly evolving therapeutic landscape, where ADCs offer both safer alternatives and opportunities for next-generation precision strategies in TNBC.