Events Details
Jazz Pharmaceuticals Announces Approval of Ziihera Regimens for Advanced HER2-Positive Gastroesophageal Cancer
Wednesday, August 26, 2026
Jazz Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has approved two Ziihera® (zanidatamab-hrii)-based treatment regimens for the first-line treatment of adults with unresectable, locally advanced or metastatic HER2-positive (HER2+) gastroesophageal adenocarcinoma (GEA).
The first regimen combines Ziihera with Tevimbra® (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive tumours classified as IHC 3+ or IHC 2+/ISH+. The second combines Ziihera with fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive IHC 3+ tumours.
The approvals are based on results from the Phase 3 HERIZON-GEA-01 trial. The study evaluated Ziihera-based combinations against trastuzumab plus chemotherapy in patients with HER2-positive advanced GEA.
In the overall HER2-positive population, both Ziihera-based regimens significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 35%. Median PFS increased to 12.4 months compared with 8.1 months with trastuzumab plus chemotherapy.
Ziihera combined with tislelizumab-jsgr and chemotherapy also produced a significant overall survival benefit. The risk of death was reduced by 28%, with median overall survival reaching 26.4 months compared with 19.2 months for trastuzumab plus chemotherapy. The result represents an improvement of more than seven months.
The PFS and overall survival benefits were generally consistent across key subgroups, including geographic region and PD-L1 status. This suggests that the combination may provide benefits across patients with different PD-L1 profiles.
The safety profile of the Ziihera-based regimens was consistent with previous studies of zanidatamab. Diarrhoea was the most frequently reported adverse reaction and generally occurred early during treatment. Loperamide was used as preventive treatment during the first cycle, while additional antidiarrhoeal treatment and treatment adjustments were used when required.
GEA includes cancers of the stomach, gastroesophageal junction and oesophagus. It is the fifth most common cancer worldwide, and around 20% of patients have HER2-positive disease. Metastatic GEA continues to have a poor prognosis, highlighting the need for additional treatment options.
Ziihera is a bispecific antibody that targets HER2 by binding to two different sites on the receptor. This activity promotes HER2 internalisation and can reduce HER2 expression on tumour cells. It also activates immune mechanisms that contribute to tumour growth inhibition and cell death.
In the US, Ziihera is now approved for the first-line treatment of adults with HER2-positive locally advanced or metastatic GEA in combination with tislelizumab-jsgr and fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ and IHC 2+/ISH+ disease. It is also approved with fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ disease.
Ziihera is also approved in the US for adults with previously treated, unresectable or metastatic HER2-positive biliary tract cancer with IHC 3+ disease.
The FDA has granted Breakthrough Therapy and Fast Track designations to zanidatamab for several potential uses, including HER2-positive GEA, biliary tract cancer and colorectal cancer. The drug is being developed by Jazz Pharmaceuticals and BeOne Medicines under licensing agreements with Zymeworks, which originally developed the molecule.
The US prescribing information for Ziihera includes boxed warnings for severe diarrhoea and embryo-fetal toxicity. Ziihera may also cause left ventricular dysfunction and infusion-related reactions. Patients receiving the treatment require appropriate monitoring and management of these risks.
The latest FDA approval expands the use of Ziihera in first-line HER2-positive advanced GEA and provides additional treatment options for patients with this difficult-to-treat form of cancer.
Source: jazzpharma.com
