In the BEGONIA platform trial, durvalumab combined with trastuzumab deruxtecan (T-DXd) produced unusually deep and durable responses in women with HER2-low metastatic breast cancer as first-line therapy. The phase 1b/2 results highlight a potential synergy between an immune checkpoint inhibitor and an antibody-drug conjugate delivering cytotoxic payloads. The study’s early signal matters for HER2-low patients, a subgroup where treatment options have historically been shaped by ADC eligibility and response durability. BEGONIA’s design also reflects the increasing trend toward multi-agent regimens to extend the benefit window after conventional chemotherapy. With phase 1b/2 data, the next step will be larger confirmatory evaluation, but the magnitude and durability of responses reported so far have already put the combination on the radar for future late-stage testing.