Dublin, Ireland, August 25, 2026
Jazz Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved two Ziihera® (zanidatamab-hrii)-containing regimens for the first-line treatment of adults with unresectable, locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). The approval includes Ziihera plus Tevimbra® (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2 IHC 3+ or IHC 2+/ISH+ disease, regardless of PD-L1 status, as well as Ziihera plus chemotherapy for patients with HER2 IHC 3+ disease. The regulatory decision expands the role of Ziihera into first-line HER2-positive GEA and establishes an important new treatment option for patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinom
FDA Approval Expands First-Line HER2+ GEA Treatment
The FDA approval is based on results from the Phase 3 HERIZON-GEA-01 trial, which evaluated Ziihera-containing regimens against trastuzumab plus chemotherapy in previously untreated advanced or metastatic HER2-positive GEA. The approval is particularly significant because the Ziihera combination with tislelizumab and chemotherapy demonstrated benefit across major patient subgroups, including those with different PD-L1 expression levels. Jazz stated that the approval makes Ziihera the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2-positive advanced GEA patients regardless of PD-L1 status. The decision also provides physicians with an additional first-line treatment approach in a disease where advanced-stage outcomes remain challenging and treatment options have historically been limited.
Ziihera Regimen Delivers 26.4-Month Median Survival
Data supporting the approval showed that Ziihera plus tislelizumab and chemotherapy produced a median overall survival of 26.4 months, compared with 19.2 months for trastuzumab plus chemotherapy, representing more than seven months of improvement. The regimen also achieved a median progression-free survival of 12.4 months versus 8.1 months, reducing the risk of disease progression or death by 35%. The overall survival benefit corresponded to a 28% reduction in the risk of death compared with the control regimen. Jazz highlighted that the 26.4-month median overall survival represents the longest median overall survival reported in a Phase 3 trial in HER2-positive advanced GEA. Benefits were generally consistent across prespecified subgroups, including PD-L1-positive and PD-L1-negative patients, supporting the broad application of the approved regimen.
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Ziihera Adds Bispecific HER2 Targeting to GEA Care
Ziihera is a bispecific HER2-directed antibody designed to bind two extracellular sites on the HER2 receptor, promoting receptor internalization and reducing HER2 expression on tumor cells. Its activity also includes complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, providing multiple mechanisms for targeting HER2-positive cancer cells. The FDA decision further strengthens zanidatamab’s development across HER2-expressing solid tumors and follows previous regulatory progress in biliary tract cancer. The approval also reflects the importance of identifying HER2 status at diagnosis in advanced or metastatic GEA because treatment selection increasingly depends on molecular characterization. While the efficacy findings support the regimen’s clinical value, safety remains an important consideration, with diarrhea identified as a prominent adverse reaction and the U.S. prescribing information carrying boxed warnings for severe diarrhea and embryo-fetal toxicity. Jazz and its development partner BeOne Medicines are continuing the broader development of zanidatamab in additional HER2-driven cancers, positioning the therapy as an increasingly important component of targeted oncology treatment..
Source: Jazz Pharmaceuticals press relese
