FDA Accepts Application for Ziihera Combinations in HER2-Positive Gastroesophageal Cancer

The U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application for Ziihera (zanidatamab) containing combinations to treat adult patients with HER2-positive unresectable locally advanced or metastatic gastric, gastroesophageal junction or gastroesophageal adenocarcinoma, according to an April 27, 2026 press release from Jazz Pharmaceuticals. The application has been granted Priority Review, with a target action date of August 25, 2026, and is based on results from the HERIZON-GEA-01 trial, which evaluated this approach as a first treatment for patients with cancer in this setting.

Study results show benefit of Ziihera combinations for patients with HER2-positive gastroesophageal cancer

The application is supported by findings from the HERIZON-GEA-01 trial, which studied Ziihera in combination with standard chemotherapy, with or without the immunotherapy drug tislelizumab.

According to the press release, patients who received Ziihera with chemotherapy experienced improved outcomes, and adding tislelizumab to this combination further enhanced clinical benefit. Importantly, the treatment approach showed effectiveness in patients whose tumors were PD-L1–positive as well as those whose tumors were PD-L1–negative. This means the combination may work for a broader group of patients with HER2-positive gastroesophageal adenocarcinoma.

The FDA also granted breakthrough therapy designation to this treatment combination. This designation is intended to speed up the development and review of treatments that may offer meaningful improvement over currently available options, especially for serious conditions where new therapies are needed.

The application is being reviewed under the FDA’s Real-Time Oncology Review program, which is designed to help bring effective treatments to patients sooner by allowing earlier review of clinical data.

HERIZON-GEA-01 trial details: Who was included and how the study was conducted?

HERIZON-GEA-01 is a global, randomized, open-label phase 3 clinical trial that compared Ziihera-based combinations with trastuzumab plus chemotherapy as a first-line treatment.

The study included 914 patients from about 300 sites across more than 30 countries. All patients had HER2-positive gastroesophageal adenocarcinoma that was unresectable, locally advanced, recurrent or metastatic. These cancers included those of the stomach, esophagus and gastroesophageal junction.

To be eligible, patients’ tumors had to meet specific HER2 testing criteria, either showing strong HER2 expression or a confirmed positive result through additional testing.

Patients were assigned to one of three treatment groups: Ziihera plus chemotherapy and tislelizumab, Ziihera plus chemotherapy, or trastuzumab plus chemotherapy. Researchers are evaluating how long patients live without their disease worsening, called progression-free survival, and overall survival.

Results from this trial were presented in January 2026 at the ASCO Gastrointestinal Cancers Symposium.

Side effects of Ziihera: What patients should know about safety?

Ziihera has several known side effects that patients and caregivers should be aware of.

The treatment can cause harm to a developing fetus. Patients who are pregnant or may become pregnant are advised to avoid this treatment and use effective birth control during treatment and for 4 months after the last dose.

Heart-related side effects have been reported. In clinical studies, 4.3% of patients experienced a decrease in heart function, and 0.9% had side effects that led to stopping treatment. Doctors may monitor heart function before and during treatment.

Infusion-related reactions are also common. These occurred in 31% of patients, with most happening on the first day of treatment. Nearly all of these reactions resolved within one day. Patients are typically given medications before treatment to help prevent these reactions, and they are closely monitored during infusions.

Diarrhea is another frequently reported side effect, affecting 48% of patients, with 6% experiencing more severe cases. Doctors may recommend medications and tests to manage this side effect.

In a study of patients with HER2-positive biliary tract cancer, serious side effects occurred in 53% of patients. These included conditions such as infection, pneumonia, biliary obstruction, diarrhea and fatigue. A fatal case of liver failure was also reported.

The most common side effects seen in at least 20% of patients included diarrhea, infusion-related reactions, abdominal pain and fatigue.

References

1. “HERIZON-GEA-01 Trial” by Dr. Rob Iannone, et al., ASCO Gastrointestinal Cancers Symposium.
2. “Jazz Pharmaceuticals Announces FDA Acceptance and Priority Review of Supplemental Biologics License Application for Ziihera (zanidatamab-hrii) Combinations in First-Line HER2+ Locally Advanced or Metastatic GEA” by Jazz Pharmaceuticals plc, PR Newswire.

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