Zanidatamab (HER2 bispecific) + Chemo Drives 76% ORR and 36.5-mo OS in 1L HER2-Positive GEA

Zanidatamab, a dual-epitope HER2-targeted bispecific antibody, was added to CAPOX, FP, or mFOLFOX6 in the single-arm Phase 2 NCT03929666 trial across Canada, Korea, and the USA. Among 46 treatment-naïve, HER2-positive advanced gastro-esophageal adenocarcinoma (GEA) patients (which represents ~20–23% of advanced GEA), confirmed ORR hit 76% (95% CI 60–88) and disease control 88%. After 47.9 mo median follow-up, median PFS reached 12.5 mo and median OS 36.5 mo, with DoR 18.7 mo. Grade ≥3 TRAEs occurred in 65%—predominantly diarrhea (39%, trimmed to 14% after mandatory prophylaxis) and hypokalaemia (22%); 13% discontinued zanidatamab, and no treatment-related deaths were reported. By contrast, the ToGA benchmark of trastuzumab + chemo posts ORR 47%, mPFS 6.7 mo, and mOS 13.8 mo, highlighting a ~2-fold survival gain here.

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