Dato-DXd (TROP2 ADC) extends PFS2/TFST/TSST vs chemo in 1L IO-ineligible metastatic TNBC

Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor payload (deruxtecan); in the Phase 3, open-label TROPION-Breast02 trial (NCT05374512), previously untreated locally recurrent inoperable/metastatic TNBC patients ineligible for immunotherapy were randomized 1:1 to Dato-DXd 6mg/kg Q3W vs investigator’s choice chemotherapy (nab-paclitaxel, capecitabine, eribulin, or carboplatin) (n=644; 323 vs 321). At the Aug 25, 2025 data cutoff (median follow-up 27.5 months), Dato-DXd improved post-progression and treatment-sequencing endpoints: median PFS2 15.6 vs 11.8 months (HR 0.61), TFST 10.9 vs 5.6 months (HR 0.49), and TSST 16.7 vs 12.6 months (HR 0.67); these sit on top of the already-reported primary endpoint gains (BICR PFS HR 0.57; OS HR 0.79) with ≥5-month longer median PFS and OS vs chemotherapy—where typical 1L chemo benchmarks are ~5–6 months median PFS (e.g., chemo control in KEYNOTE-355 PD-L1 CPS≥10 had median PFS 5.6 months).