T-DXd (HER2 ADC) + durvalumab (PD-L1) delivers ~83% ORR and ~38-month mPFS in 1L HER2+ mBC

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody–drug conjugate (topoisomerase I payload), combined here with durvalumab, an anti–PD-L1 antibody, as first-line therapy in the DESTINY-Breast07 Phase 1b/2 open-label platform study (NCT04538742) in previously untreated unresectable/metastatic HER2+ breast cancer after a ≥12-month disease-free interval (n=64 randomized; 63 treated; median follow-up 30.1 months; DCO January 31, 2025). Confirmed ORR was 82.8% (80% CI 75.2–88.8), median DOR 36.1 months, and median PFS 37.7 months with a 24-month PFS rate of 75.5% (OS immature/NE); by comparison, the long-standing 1L benchmark pertuzumab + trastuzumab + docetaxel in CLEOPATRA delivered ORR ~80% and mPFS 18.5 months (with mOS 56.5 months in final analysis). Safety showed expected T-DXd chemo-like toxicities (nausea 79.4%, vomiting 46.0%, neutropenia 46.0%, anemia 44.4%), Grade ≥3 AEs in 58.7%, serious AEs in 30.2%, and 2 AE-related deaths (sepsis/septic shock); adjudicated drug-related ILD/pneumonitis occurred in 17.5% (Grade 3 in 3.2%) with no fatal ILD.