T-DXd (HER2 ADC) + rilvegostomig (PD-1×TIGIT) + fluoropyrimidine delivers 70% ORR as 1L HER2+ gastroesophageal triplet

Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody–drug conjugate (topoisomerase I payload) and rilvegostomig is an Fc-reduced PD-1×TIGIT bispecific antibody; DESTINY-Gastric03 Part 4 arm A (NCT04379596) tested 1L T-DXd + rilve + fluoropyrimidine (5-FU or capecitabine) in previously untreated advanced/metastatic HER2+ GC/GEJA/EA (n=30; local HER2 IHC 3+ or IHC 2+/ISH+). At the Oct 16, 2025 cutoff (median follow-up 7.6 months), confirmed investigator-assessed ORR was 70% (21/30), with higher ORR in IHC 3+ (78%; 18/23) vs IHC 2+/ISH+ (50%; 3/6) and in PD-L1 CPS ≥1 (82%; 9/11) vs CPS <1 (50%; 3/6; PD-L1 centrally assessed retrospectively). Safety included adjudicated drug-related ILD/pneumonitis in 7% (2/30; both Grade 2) and no reported drug-related left ventricular dysfunction—efficacy looks directionally similar to the established 1L benchmark of pembrolizumab + trastuzumab + chemo (ORR ~74% overall; ~76% in CPS ≥1), but cross-trial comparisons are very tentative given the tiny n and short follow-up.