Jazz’s ;The U.S. Food and Drug Administration has approved Jazz Pharmaceuticals’ Ziihera (zanidatamab-hrii) for previously untreated adults with unresectable, locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). The decision expands Ziihera into a substantially larger cancer market and introduces a new HER2-targeted option for patients with advanced cancers of the stomach, gastroesophageal junction and esophagus.
- The FDA approved Ziihera for first-line HER2-positive gastroesophageal adenocarcinoma.
- Ziihera can be used with chemotherapy and, for eligible patients, Tevimbra (tislelizumab).
- The Ziihera-Tevimbra-chemotherapy combination reduced the risk of death by 28% compared with trastuzumab plus chemotherapy.
- Median overall survival reached 26.4 months, compared with 19.2 months in the control group.
- The approval covers HER2-positive tumors regardless of PD-L1 status when Ziihera is combined with Tevimbra and chemotherapy.
- Jazz is developing Ziihera for additional cancer indications.
Ziihera Gains First-Line Approval
The FDA’s August 25 decision allows Ziihera to be used in two first-line treatment combinations.
For patients with HER2-positive, unresectable locally advanced or metastatic GEA, Ziihera can be administered with fluoropyrimidine- and platinum-based chemotherapy and tislelizumab, an immune checkpoint inhibitor marketed as Tevimbra.
The agency also approved Ziihera with the same chemotherapy backbone without Tevimbra for patients whose tumors are classified as HER2 IHC 3+.
The approval covers cancers originating in the stomach, gastroesophageal junction and esophagus.
GEA is the fifth most common cancer worldwide, according to Jazz, and approximately 20% of patients have HER2-positive disease.
Phase 3 Trial Supports the Approval
The FDA’s decision was based on results from the global HERIZON-GEA-01 Phase 3 trial, which compared Ziihera-based treatment with a regimen containing trastuzumab, the established HER2-targeted therapy.
Patients were assigned to one of three treatment groups: trastuzumab with chemotherapy, Ziihera with chemotherapy, or Ziihera combined with Tevimbra and chemotherapy.
The combination of Ziihera, Tevimbra and chemotherapy produced a statistically significant improvement in both overall survival and progression-free survival compared with the trastuzumab-based control.
Median overall survival was 26.4 months for patients receiving the Ziihera-based triplet, compared with 19.2 months for those receiving trastuzumab and chemotherapy. The treatment reduced the risk of death by 28%.
Progression-free survival also improved. Patients receiving the Ziihera triplet had a median progression-free survival of 12.4 months, compared with 8.1 months in the control group.
Approval Extends to Patients Regardless of PD-L1 Status
One of the notable aspects of the FDA decision is the broader eligibility of the Ziihera-Tevimbra-chemotherapy combination.
The regimen is approved for patients with HER2-positive tumors regardless of whether their cancer expresses PD-L1, a biomarker that can influence the use of certain immunotherapies.
Data from the HERIZON-GEA-01 trial showed an overall survival benefit in both PD-L1-positive and PD-L1-negative patients. The benefit was particularly pronounced among patients whose tumors had a tumor area positivity score below 1, according to subgroup analyses.
For this PD-L1-negative subgroup, median overall survival with the Ziihera triplet reached 29.7 months, compared with the corresponding outcome in the control group, an improvement of 13.9 months.
Ziihera Uses a Dual-Targeting Mechanism
Ziihera is a bispecific HER2 antibody, meaning it is designed to bind two separate sites on the HER2 receptor.
The drug targets extracellular domains 2 and 4 of HER2. By binding to two different HER2 receptors, Ziihera promotes receptor clustering, a mechanism that can help trigger cancer cell death and enhance immune activity.
The drug’s design distinguishes it from traditional HER2-targeted antibodies such as trastuzumab, which has been a standard component of first-line treatment for HER2-positive gastroesophageal cancer for more than a decade.
Chemotherapy-Only Combination Shows Mixed Results
The FDA also approved Ziihera in combination with chemotherapy for patients with HER2 IHC 3+ tumors.
In the clinical trial, this treatment combination significantly improved progression-free survival compared with trastuzumab and chemotherapy. Median progression-free survival for the Ziihera group was 14.2 months, compared with 7.6 months for the control group among patients with IHC 3+ tumors.
However, the overall survival analysis for this Ziihera-and-chemotherapy combination had not demonstrated a statistically significant benefit at the interim analysis used for the FDA review. The company expects another interim overall survival analysis later this year.
Safety Warnings Accompany Approval
The FDA-approved labeling includes a boxed warning for diarrhea and embryo-fetal toxicity.
The prescribing information also contains warnings concerning left ventricular dysfunction and infusion-related reactions.
Tevimbra carries separate warnings related to immune-mediated adverse reactions, infusion-related reactions, complications associated with allogeneic stem cell transplantation and embryo-fetal toxicity.
Patients receiving the approved regimens will therefore require monitoring for treatment-related complications as part of their cancer care.
Jazz Targets a Larger Market
The approval represents a major expansion for Ziihera, which previously received FDA approval for a different cancer indication involving HER2-positive biliary tract cancer.
The gastroesophageal cancer market is considerably larger. Jazz estimates that around one-fifth of GEA patients have HER2-positive disease, creating a significant potential patient population for the drug.
Analysts cited by Fierce Pharma have estimated that Ziihera could eventually generate around $1.5 billion in peak sales from GEA alone, while Jazz has set a broader peak-sales target of more than $2 billion across all indications.
Further Cancer Studies Underway
Jazz is continuing to evaluate Ziihera across additional cancer types.
The company is studying the drug in HER2-positive breast cancer among patients who have previously received other HER2-directed treatments. A separate basket trial is assessing Ziihera across multiple tumor types, while Jazz is also discussing potential development in colorectal cancer with the FDA.
Jazz has also indicated that it is considering testing Ziihera in earlier-stage gastric cancer, where there is currently no approved HER2-targeted treatment in that setting.
The FDA approval gives Jazz a broader role in HER2-positive gastroesophageal cancer and provides physicians with a new first-line treatment option supported by Phase 3 survival data.
Ziihera has received U.S. FDA approval for two first-line treatment regimens for adults with unresectable, locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA).
Jazz’s Ziihera Wins FDA Nod for First-Line Cancer Care
Jazz’s Ziihera has received U.S. FDA approval for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). The approval covers two treatment combinations involving zanidatamab-hrii, the active ingredient in Ziihera.
Jazz’s Ziihera Expands Into First-Line Treatment
Jazz’s Ziihera is now approved in combination with tislelizumab and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive disease identified as IHC 3+ or IHC 2+/ISH+. It is also approved with chemotherapy alone for patients whose tumors are HER2 IHC 3+.
Jazz’s Ziihera Targets HER2
Jazz’s Ziihera is a bispecific antibody designed to target two extracellular sites on the HER2 protein. By binding HER2, the therapy can promote receptor internalization and activate immune-mediated mechanisms that contribute to tumor-cell destruction.
Jazz’s Ziihera Supported by Phase 3 Data
The approval was supported by results from the Phase 3 HERIZON-GEA-01 trial. The study compared Ziihera-based regimens with trastuzumab plus chemotherapy in patients with advanced HER2-positive gastroesophageal adenocarcinoma.
Jazz’s Ziihera Shows Survival Benefit
Updated results announced on August 31, 2026, showed that Ziihera combined with chemotherapy produced a statistically significant and clinically meaningful overall-survival improvement compared with trastuzumab plus chemotherapy.
Earlier Phase 3 results reported a median overall survival of 26.4 months for the Ziihera, tislelizumab, and chemotherapy combination compared with 19.2 months for trastuzumab plus chemotherapy.
Jazz’s Ziihera Broadens Treatment Options
Jazz’s Ziihera provides another HER2-targeted approach for patients with advanced gastroesophageal adenocarcinoma. The approval also allows the tislelizumab-containing regimen for eligible HER2-positive patients regardless of PD-L1 status.
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