Dublin, Ireland, and Madrid, Spain, October 23, 2026
Jazz Pharmaceuticals has reported sustained three-year survival outcomes for Ziihera® (zanidatamab-hrii)-based combinations in adults with HER2-positive advanced gastroesophageal adenocarcinoma (GEA). Updated results from the Phase 3 HERIZON-GEA-01 trial, presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, showed that the combination of Ziihera, tislelizumab and chemotherapy achieved a median overall survival of 27 months. Nearly 40% of patients receiving this combination were estimated to be alive three years after treatment began. The study also demonstrated a statistically significant overall survival benefit for Ziihera combined with chemotherapy compared with trastuzumab plus chemotherapy, an established HER2-directed treatment approach. These findings provide further evidence supporting Ziihera-based regimens for first-line treatment of eligible patients with unresectable locally advanced or metastatic HER2-positive GEA. Ziihera received U.S. Food and Drug Administration (FDA) approval for the relevant first-line treatment regimens in August 2026.
Phase 3 Trial Demonstrates Sustained Survival Benefits
The updated findings came from the global, randomized HERIZON-GEA-01 Phase 3 clinical trial, which enrolled 914 patients across approximately 225 sites in more than 30 countries. The study compared Ziihera plus chemotherapy and tislelizumab, Ziihera plus chemotherapy alone, and trastuzumab plus chemotherapy in previously untreated advanced HER2-positive GEA. At a median follow-up of 35.3 months, the combination of Ziihera, tislelizumab and chemotherapy achieved a median overall survival of 27.0 months, compared with 19.6 months for trastuzumab plus chemotherapy. This represented a 35% reduction in the risk of death, based on a hazard ratio of 0.65. The estimated three-year overall survival rate was 39.8% for the Ziihera, tislelizumab and chemotherapy combination, compared with 31.5% for Ziihera plus chemotherapy and 22.9% for trastuzumab plus chemotherapy. These findings suggest that the addition of immunotherapy to the Ziihera-based regimen may provide a meaningful long-term survival advantage. However, the difference in overall survival between the two Ziihera-containing regimens did not reach conventional statistical significance in this analysis.
Ziihera Plus Chemotherapy Shows Significant Improvement
The trial also demonstrated a statistically significant survival benefit for Ziihera plus chemotherapy compared with trastuzumab plus chemotherapy. Median overall survival reached 22.9 months with Ziihera and chemotherapy, compared with 19.6 months in the trastuzumab-based control group. The combination reduced the risk of death by 24%, with a hazard ratio of 0.76 and a reported P-value of 0.0088. These results are important because patients with advanced HER2-positive gastroesophageal adenocarcinoma often face substantial treatment challenges and limited long-term survival prospects. GEA includes cancers originating in the stomach, gastroesophageal junction and esophagus. HER2 is a protein involved in cell growth and is overexpressed in a subset of these cancers, making it a relevant target for precision oncology. The trial findings support Ziihera as an additional HER2-directed treatment option and have contributed to its inclusion in preferred treatment recommendations for eligible patients. Nevertheless, treatment selection requires consideration of tumor characteristics, approved indications, patient health and the potential risks associated with each regimen.
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Bispecific HER2 Antibody Supports Targeted Cancer Therapy
Ziihera is a bispecific antibody that targets two distinct extracellular sites on the HER2 receptor, enabling it to interfere with HER2 signaling and promote immune-mediated destruction of tumor cells. Its mechanisms include receptor internalization, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity. Tislelizumab, marketed as Tevimbra®, is a PD-1 immune checkpoint inhibitor that helps restore antitumor immune activity, while chemotherapy attacks rapidly dividing cancer cells through complementary mechanisms. Combining these approaches is intended to strengthen treatment activity through multiple biological pathways. The updated trial results showed that the safety profiles of the Ziihera-containing combinations remained consistent with earlier analyses. However, the medicine carries important risks, including potentially severe diarrhea and embryo-fetal toxicity, and treatment requires appropriate monitoring. Ziihera is approved in the United States for specified first-line HER2-positive advanced GEA regimens and for certain previously treated HER2-positive biliary tract cancers. The new survival findings strengthen the evidence supporting its role in oncology, while ongoing clinical experience and regulatory oversight will continue to define its use. The results represent a significant development in HER2-positive cancer treatment, but individual outcomes can vary and treatment decisions must be made with qualified healthcare professionals.
Source: Jazz Pharmaceuticals press release
