FDA approves Ziihera-based regimens for first-line HER2+ gastroesophageal cancer

Jazz Pharmaceuticals announced on August 25, 2026 that the FDA approved two Ziihera® (zanidatamab-hrii)-containing regimens for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma. The approvals cover Ziihera plus Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ and IHC 2+/ISH+ disease, and Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ disease alone.¹

The approval rests on the Phase 3 "HERIZON-GEA-01" trial. Results were published in the New England Journal of Medicine and first presented at ASCO GI 2026, with PD-L1 subgroup data shown at ASCO 2026.¹ On progression-free survival, both Ziihera combinations cut the risk of disease progression or death by 35%, pushing median PFS to 12.4 months compared with 8.1 months for trastuzumab plus chemotherapy.¹ For overall survival, the Ziihera-tislelizumab-chemotherapy arm lowered the risk of death by 28% versus trastuzumab plus chemotherapy, with median OS reaching 26.4 months against 19.2 months, a gain of more than seven months and the longest median OS reported in a Phase 3 trial in this setting.¹ Jazz said the PFS and OS benefits held up across major prespecified subgroups, including region and PD-L1 status.¹

On safety, diarrhea was the most common adverse reaction, typically occurring early, and was managed with loperamide prophylaxis in cycle one plus antidiarrheals and dose adjustments, leading to few Ziihera discontinuations.¹ The U.S. label carries boxed warnings for diarrhea and embryo-fetal toxicity.¹

The trial is continuing, with additional analyses planned.¹ Jazz said it will host an investor webcast the same day to discuss the approval and update its zanidatamab development program.