FDA approves Ziihera regimens for first-line HER2-positive gastroesophageal cancer

On August 25, 2026, FDA approved two Ziihera (zanidatamab-hrii) regimens for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma.

Under the new approval, Ziihera may be used in two first-line regimens. Ziihera plus Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy is approved for tumors with strong HER2 protein expression on immunohistochemistry (IHC 3+) or moderate expression with HER2 gene amplification confirmed by in situ hybridization (IHC 2+/ISH+). The regimen can be used regardless of PD-L1 expression, a biomarker often used to determine eligibility for immunotherapy. Ziihera plus chemotherapy without tislelizumab is approved only for tumors with strong HER2 expression (IHC 3+). HER2 status must be confirmed with an FDA-approved test.

The approval introduces the first bispecific HER2-directed antibody into front-line treatment for this disease. Ziihera binds two sites on HER2, promoting receptor removal from the tumor-cell surface and activating immune-mediated tumor-cell killing.

In the phase 3 HERIZON-GEA-01 trial, Ziihera plus tislelizumab and chemotherapy extended median overall survival to 26.4 months, compared with 19.2 months for trastuzumab plus chemotherapy, reducing the risk of death by 28%. Median progression-free survival was 12.4 versus 8.1 months. Benefits were observed in both PD-L1–positive and PD-L1–negative tumors.

Among patients with IHC 3+ tumors, Ziihera plus chemotherapy extended median progression-free survival to 14.2 months versus 7.6 months with trastuzumab plus chemotherapy. For the overall trial population, however, the overall survival comparison did not reach statistical significance at the interim analysis.

Ziihera carries a boxed warning for severe diarrhea and embryo-fetal toxicity. Loperamide prophylaxis is required during cycle 1, and clinicians should also monitor for left ventricular dysfunction and infusion-related reactions.

“This approval is a major step forward for people with HER2+ advanced GEA. Ziihera is now the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2+ advanced GEA patients, regardless of PD-L1 status, establishing a new standard of care in first-line treatment,” said Rob Iannone, MD, chief medical officer of Jazz Pharmaceuticals. “The HERIZON-GEA-01 results include the longest median overall survival reported in a Phase 3 trial in this setting, at 26.4 months.”

Source: Jazz Pharmaceuticals. (2026 Aug 25). U.S. FDA approves Ziihera (zanidatamab-hrii) with and without tislelizumab plus chemotherapy in first-line HER2-positive advanced gastroesophageal adenocarcinoma