BeOne Medicines Reports Positive Second Interim Survival Data for Ziihera in HER2+ Gastroesophageal Cancer

BeOne Medicines and Jazz Pharmaceuticals announced positive topline results from the second interim analysis (IA2) of the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera (zanidatamab), in combination with chemotherapy, with and without Tevimbra (tislelizumab), as first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA).¹ At IA2, Ziihera plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with trastuzumab plus chemotherapy, meeting the trial's remaining primary endpoint.¹ IA2 also provided longer follow-up data for the Tevimbra plus Ziihera and chemotherapy regimen, showing an improved OS hazard ratio and continued durable outcomes.¹ The safety profile of both Ziihera-containing regimens at IA2 was generally consistent with IA1, with no new safety signals identified.¹ The results have been submitted for presentation at a major medical meeting in the fourth quarter of 2026.¹

How does this build on the recent FDA approval?

The IA2 data arrive days after the FDA approved supplemental Biologics License Applications for both Ziihera and Tevimbra in combination with chemotherapy for first-line treatment of HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma, making it the first FDA-approved immunotherapy-based regimen in this setting to demonstrate median OS exceeding two years regardless of PD-L1 status.¹ That approval was based on IA1 results, which were published earlier this year in the New England Journal of Medicine and showed benefit across both PD-L1 and HER2+ expression levels.¹ Mark Lanasa, M.D., Ph.D., chief medical officer, solid tumors at BeOne Medicines, said in a press release, "Today's results, coming just days after FDA approval of the HERIZON-GEA-01 regimens, add to a series of important milestones demonstrating their potential to transform the treatment of HER2-positive GEA. We now have compelling phase 3 evidence of statistically significant and clinically meaningful overall survival results across both HERIZON-GEA experimental arms, reinforcing the opportunity to improve outcomes for patients beginning first-line treatment."¹

How does Ziihera work?

Ziihera is a bispecific HER2-directed antibody that binds two distinct extracellular sites on HER2 simultaneously.² Binding drives internalization and a reduction in HER2 expression on the tumor cell surface, while also inducing complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, mechanisms that together produce tumor growth inhibition and cell death.² Zanidatamab is developed by Jazz Pharmaceuticals and BeOne Medicines under separate license agreements with Zymeworks, which discovered the molecule; BeOne holds rights in Asia (excluding India and Japan), Australia, and New Zealand, while Jazz holds rights elsewhere.²

Bispecific antibodies remain a small share of the biologics approved to date relative to what's advancing through earlier-phase pipelines. "Within the FDA-approved products, there's a minimal amount right now that … are bispecifics. However, when you look at the pipeline of products that are coming through in phase 1, phase 2, there's an enormous wave of these complex proteins that are coming through," said Atul Mohindra, head of biologics R&D at Lonza, in earlier BioPharm International^© coverage of the bispecific antibody field broadly — a manufacturing-focused interview unrelated to zanidatamab or this trial specifically.⁴

Why does this matter for GEA patients?

GEA, encompassing cancers of the stomach, gastroesophageal junction, and esophagus, represents the fifth (stomach) and eighth (esophageal) most common cancers worldwide.³ Roughly 20% of GEA patients have HER2-positive disease.⁵ Once advanced, GEA carries a poor prognosis, with cure remaining rare outside of localized disease.³ HERIZON-GEA-01 randomized 914 patients across approximately 300 sites in more than 30 countries, comparing Ziihera plus chemotherapy, with and without Tevimbra, against trastuzumab plus chemotherapy, the prior standard of care.¹

What happens next?

Full IA2 data, including hazard ratios and confidence intervals not yet disclosed in the topline announcement, are expected at a major medical meeting in the fourth quarter of 2026.¹ HERIZON-GEA-01 continues with further analyses planned.

References

1. BeOne Medicines Ltd. BeOne Medicines Announces New Phase 3 Survival Data Reinforcing Benefit of ZIIHERA-Containing Regimens in First-Line HER2+ Gastroesophageal Cancer. Press release. Published August 31, 2026. Accessed September 1, 2026.
2. BeOne Medicines Ltd. About ZIIHERA (zanidatamab-hrii). Included in reference 1 above.
3. Bartley AN, Washington MK, Ventura CB, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. Published online October 2016.
4. Mohindra A. The Challenges, Successes, and Future of Bispecific Antibodies. BioPharm International. Published December 17, 2024. Accessed September 1, 2026.
5. Abrahao-Machado, L. F., & Scapulatempo-Neto, C. (2016). HER2 testing in gastric cancer: An update. World journal of gastroenterology, 22(19), 4619–4625. https://doi.org/10.3748/wjg.v22.i19.4619.