Datopotamab deruxtecan in Chinese patients with heavily pretreated advanced or metastatic triple-negative breast cancer in the phase I/II TROPION-PanTumor02 study

Background: Despite recent improvements in treatment, outcomes for patients with pretreated, advanced triple-negative breast cancer (TNBC) remain poor. We present results from the phase I/II TROPION-PanTumor02 study of datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate (ADC) comprised of a humanised anti-trophoblast cell surface antigen 2 (TROP2) monoclonal antibody conjugated to a potent topoisomerase I (Topo-I) inhibitor, in Chinese patients with pretreated, advanced TNBC. Methods: Patients received Dato-DXd 6 mg/kg intravenously every 3 weeks until radiological progression or another discontinuation criterion was met. The primary endpoint was objective response rate (ORR) per independent central review (ICR); secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: At data cutoff (6 May 2024), 79 patients had received treatment. Median age was 50.0 years (range, 33-73 years) and 74 (93.7%) patients had metastatic disease; 33 (41.8%) had liver metastases. Patients had received a median of 3 (range, 2‒8) prior lines of chemotherapy for advanced disease [≥5 lines, n=21 (26.6%)]. ORR by ICR was 33.8% [95% confidence interval (CI): 23.4-45.4%]. Median PFS and OS were 5.3 months (95% CI: 4.2-6.9) and 13.5 months [95% CI: 10.7-not calculable (NC)], respectively. The most common treatment-related adverse events (TRAEs) were stomatitis (49.4%) and nausea (43.0%). Twenty-five patients (31.6%) experienced grade ≥ III TRAEs. Adjudicated drug-related interstitial lung disease (ILD) was reported in 1 patient (grade II). Conclusions: Dato-DXd monotherapy demonstrated clinical activity and manageable safety in Chinese patients with heavily pretreated, advanced TNBC. Phase III studies of Dato-DXd alone or in combination in early-stage and advanced TNBC are ongoing.