Durvalumab (PD-L1) + trastuzumab deruxtecan (HER2 ADC) delivers 62% ORR but 21% ILD in 1L HR−/HER2-low mBC

Durvalumab is an anti–PD-L1 checkpoint inhibitor and trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor payload; the combo was tested as first-line therapy in arm 6 of the multicenter, open-label Phase 1b/2 BEGONIA platform trial (NCT03742102) in locally advanced unresectable or metastatic HR-negative, HER2-low breast cancer (n=58; median follow-up 20.6 months). ORR was 62.1% (95% CI 48.4-74.5), missing the protocol bar of 66.6% responses, with median DoR 15.2 months, median PFS 12.6 months, and median OS 30.3 months; for a rough SOC benchmark in PD-L1 CPS≥10 metastatic TNBC, pembrolizumab + chemo has reported median PFS ~9.7 months (vs ~5.6 months with chemo alone), so the observed PFS here looks directionally competitive albeit cross-trial and in a biomarker-defined HER2-low subset. Safety was described as consistent with the single agents, but adjudicated drug-related ILD/pneumonitis was 20.7% (grade 1-2: 19.0%; grade 5: 1.7%), which is a material “cost of admission” when compared with chemo/IO backbones that do not carry T-DXd’s characteristic ILD risk.