Ziihera (zanidatamab-hrii) plus chemotherapy significantly improved overall survival compared with trastuzumab plus chemotherapy as first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma, according to new Phase 3 HERIZON-GEA-01 data announced by Jazz Pharmaceuticals and BeOne Medicines.
The findings come from the second interim analysis of the global Phase 3 trial and provide further evidence supporting Ziihera-containing regimens in the first-line treatment of HER2-positive gastroesophageal adenocarcinoma.
Ziihera Shows Significant Overall Survival Benefit
At the second interim analysis, Ziihera plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with trastuzumab plus chemotherapy, meeting the remaining primary endpoint analysis of HERIZON-GEA-01.
The OS hazard ratio for Ziihera plus chemotherapy also improved compared with the first interim analysis, although detailed survival figures from the updated analysis have not yet been disclosed.
The safety profile remained generally consistent with previously reported HERIZON-GEA-01 findings and the known profiles of the individual treatments, with no new safety signals identified.
The results provide Phase 3 evidence supporting Ziihera as an alternative HER2-targeted backbone to trastuzumab in the first-line setting.
Longer Follow-Up Supports Ziihera Plus Tislelizumab and Chemotherapy
The second interim analysis also provided longer follow-up for patients receiving Ziihera plus Tevimbra (tislelizumab-jsgr) and chemotherapy. The regimen demonstrated an improved OS hazard ratio compared with the first interim analysis, alongside continued durable outcomes.
Earlier HERIZON-GEA-01 results had already demonstrated statistically significant improvements in both progression-free survival and overall survival with the three-drug regimen. The survival benefit was observed across PD-L1 and HER2 expression levels.
These findings further reinforce the clinical benefit of combining HER2-targeted therapy with PD-1 inhibition and chemotherapy in first-line HER2-positive gastroesophageal adenocarcinoma.
FDA Recently Approved Both Ziihera Regimens
The updated survival results follow the August 25, 2026 FDA approval of Ziihera-containing regimens in this setting.
The FDA approved Ziihera plus tislelizumab and chemotherapy for the first-line treatment of adults with HER2-positive, unresectable locally advanced or metastatic gastroesophageal adenocarcinoma with IHC 3+ or IHC 2+/ISH+ tumors.
Ziihera plus chemotherapy was also approved as first-line treatment for patients with HER2-positive IHC 3+ disease.
According to BeOne Medicines, the Ziihera, tislelizumab and chemotherapy combination became the first FDA-approved immunotherapy-based regimen in this setting to demonstrate a median overall survival exceeding two years, regardless of PD-L1 status.
About HERIZON-GEA-01
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial conducted jointly by Jazz Pharmaceuticals and BeOne Medicines.
The study enrolled 914 patients across more than 30 countries with unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma.
Patients were randomized to receive:
- Ziihera plus chemotherapy and tislelizumab
- Ziihera plus chemotherapy
- Trastuzumab plus chemotherapy
Eligible tumors were defined as HER2 IHC 3+ or IHC 2+/ISH-positive by central assessment.
The study’s dual primary endpoints are progression-free survival assessed by blinded independent central review and overall survival.
Gastroesophageal adenocarcinoma includes adenocarcinomas of the stomach, gastroesophageal junction, and esophagus. Approximately 20% of patients have HER2-positive disease, while outcomes for patients with metastatic disease remain poor.
HERIZON-GEA-01 Updates: Zanidatamab ± Tislelizumab in HER2-Positive Gastroesophageal Cancer
Full Results Expected in Late 2026
The updated second interim analysis results have been submitted for presentation at a major medical meeting in the fourth quarter of 2026.
Jazz Pharmaceuticals also plans to submit the new data to health authorities globally as the companies continue development of zanidatamab-based treatment strategies.
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