FDA Approvals
FDA Approves Ziihera With and Without Tislelizumab Plus Chemotherapy for First-Line HER2-Positive Gastroesophageal Adenocarcinoma

FDA Approves Ziihera With and Without Tislelizumab Plus Chemotherapy for First-Line HER2-Positive Gastroesophageal Adenocarcinoma

Vahe Grigoryan By Vahe Grigoryan, MD, Editorial Director at OncoDaily Aug 25, 2026
Nare Hovhannisyan Fact checked by Nare Hovhannisyan, MD, Content Creator and Medical Writer at OncoDaily Aug 25, 2026
Elen Baloyan Medically reviewed by Elen Baloyan, MD, Medical Oncologist, Managing Editor of OncoDaily Aug 25, 2026

The U.S. Food and Drug Administration (FDA) has approved two Ziihera (zanidatamab-hrii)-containing regimens for the first-line treatment of adults with HER2-positive unresectable locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). The approval was announced by Jazz Pharmaceuticals on August 25, 2026.

The approval includes:

  • Ziihera plus Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive tumors classified as IHC 3+ or IHC 2+/ISH+.
  • Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2 IHC 3+ tumors.

Gastroesophageal adenocarcinoma in this indication includes cancers of the stomach, gastroesophageal junction, and esophagus. The Ziihera plus tislelizumab and chemotherapy regimen is approved across the eligible HER2-positive population regardless of PD-L1 status.

HERIZON-GEA-01 Trial Supports FDA Approval

The approval is supported by results from the randomized, open-label Phase 3 HERIZON-GEA-01 trial (NCT05152147), which evaluated zanidatamab-based treatment as first-line therapy for previously untreated HER2-positive advanced gastroesophageal adenocarcinoma.

A total of 914 patients were randomized in a 1:1:1 ratio to receive:

  • zanidatamab plus tislelizumab and chemotherapy;
  • zanidatamab plus chemotherapy; or
  • trastuzumab plus chemotherapy.

At a median follow-up of 25.9 months, median progression-free survival (PFS) was 12.4 months in both zanidatamab-containing groups, compared with 8.1 months with trastuzumab plus chemotherapy.

For patients receiving zanidatamab plus tislelizumab and chemotherapy, the hazard ratio for disease progression or death was 0.63, corresponding to a 37% reduction in risk compared with trastuzumab plus chemotherapy.

For zanidatamab plus chemotherapy, the hazard ratio was 0.65, representing a 35% reduction in the risk of progression or death. Both PFS comparisons were statistically significant.

Overall Survival Reaches 26.4 Months With Ziihera, Tislelizumab and Chemotherapy

The combination of zanidatamab, tislelizumab, and chemotherapy also produced a statistically significant improvement in overall survival (OS). Median OS was 26.4 months with zanidatamab plus tislelizumab and chemotherapy, compared with 19.2 months with trastuzumab plus chemotherapy. The hazard ratio for death was 0.72, corresponding to a 28% reduction in the risk of death.

Median OS with zanidatamab plus chemotherapy was 24.4 months. However, at the interim analysis, the OS difference compared with trastuzumab plus chemotherapy did not reach statistical significance, with a hazard ratio of 0.80 and P value of 0.06. Additional analyses are planned as the trial continues.

The HERIZON-GEA-01 results were published in the New England Journal of Medicine in May 2026.

Safety of Ziihera-Based Regimens

Grade 3 or higher adverse events occurred in 83.3% of patients receiving zanidatamab plus tislelizumab and chemotherapy, 73.8% receiving zanidatamab plus chemotherapy, and 74.5% receiving trastuzumab plus chemotherapy.

Diarrhea was the most common grade 3 or higher adverse event, occurring in 24.8%, 20.0%, and 12.9% of patients in the three treatment groups, respectively.

The U.S. Prescribing Information for Ziihera contains boxed warnings for diarrhea and embryo-fetal toxicity.

About Ziihera

Ziihera is a bispecific HER2-targeted antibody designed to bind two distinct extracellular sites on the HER2 protein.

The drug was previously approved by the FDA in November 2024 for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test.

The latest FDA decision expands the role of zanidatamab into the first-line treatment of HER2-positive advanced gastroesophageal adenocarcinoma, providing new treatment options for patients with HER2-driven gastric, gastroesophageal junction, and esophageal cancers.

Read further on OncoDaily: Astellas Doses First Patient in Phase 3 ASP2138 Trial for CLDN18.2-Positive Gastric and GEJ Cancer

ASP2138

Vahe Grigoryan

Author

Vahe Grigoryan

MD, Editorial Director at OncoDaily

Vahe Grigoryan is a medical doctor and Editorial Director at OncoDaily, and host of the ONCOFFEE podcast. He aspires to pursue a career in oncology and is passionate about cancer medicine, scientific communication, and the people and stories shaping the field. As an Editorial Director at OncoDaily, Vahe develops original medical news and educational content covering advances in cancer research, treatment, policy, and professional development. Through the ONCOFFEE podcast, he speaks with early-career oncologists and healthcare professionals about their journeys, training challenges, and experiences in medicine. His interests include clinical oncology, cancer research, medical education, and making complex scientific information clear and accessible to the global oncology community.
Nare Hovhannisyan
Fact checked by Nare Hovhannisyan MD, Content Creator and Medical Writer at OncoDaily Nare Hovhannisyan, MD, is a radiation oncology resident at Yerevan State Medical University and the National Center of Oncology in Armenia. She is also a content creator and medical writer at OncoDaily, where she develops original articles covering radiotherapy, scientific and clinical research, oncology conferences, public health, professional awards, leadership appointments, and career developments within the global oncology community. Her work at OncoDaily includes reporting key findings from major international congresses, including ESMO, ESTRO, and ASTRO, conducting interviews with oncology professionals, and translating complex medical evidence into clear and accessible content for a professional audience. She collaborates closely with the editorial team to ensure scientific accuracy and evidence-based reporting. Nare previously gained clinical experience in medical oncology at the Mikayelyan Institute of Surgery, participating in chemotherapy administration, toxicity management, supportive care, and multidisciplinary tumour board discussions. Her professional interests include modern radiotherapy techniques, treatment planning, precision oncology, multidisciplinary cancer care, clinical research, and scientific communication. She has participated in several international educational programmes, including the ESMO Preceptorship on Practising Oncology and advanced ESMO courses in antibody–drug conjugates, genitourinary cancers, and precision oncology. She is also a co-author of the abstract “Patterns of Radiotherapy for Lymphoma in Armenia: An Analysis from 2020 to 2023,” published in *Clinical Lymphoma, Myeloma and Leukemia* in 2024.
Elen Baloyan
Medically reviewed by Elen Baloyan MD, Medical Oncologist, Managing Editor of OncoDaily Elen Baloyan is a medical oncologist, the Managing Editor of OncoDaily and the Editor-in-Chief of OncoDaily Magazine. She is a clinical research physician at the Immune Oncology Research Institute, with special focus on immunotherapy, lung cancer and global oncology. She is currently a research fellow at the BG Lab, sponsored by OncoDaily. She also serves as the Vice President of News and Content Strategy of P53 Inc..
cancer FDA FDA Approves gastroesophageal adenocarcinoma HERIZON-GEA-01 Jazz Pharmaceuticals New England Journal of Medicine OncoDaily Oncology Zanidatamab-hrii Ziihera