Zymeworks Announces Positive HERIZON-GEA-01 Phase 3 Results Supporting Ziihera® (zanidatamab-hrii) as HER2-Targeted Agent-of-Choice and New Standard of Care in First-Line HER2-Positive Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma
Zymeworks Inc. (Nasdaq: ZYME) a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, including cancer, inflammation, and autoimmune disease, today announced positive topline results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera (zanidatamab-hrii) in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra (tislelizumab), as a first-line treatment for HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma, including cancers of the stomach, gastroesophageal junction, and esophagus. The results were announced today by Zymeworks’ development and commercialization partners, Jazz Pharmaceuticals (Jazz) and BeOne Medicines (BeOne).
“We’re excited to announce positive results from the HERIZON-GEA-01 Phase 3 trial, in collaboration with Jazz Pharmaceuticals and BeOne Medicines. This pivotal study investigated our HER2-targeted bispecific antibody in first-line HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma.” – Zymeworks
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Key Findings from HERIZON-GEA-01
- Both Ziihera plus chemotherapy and Ziihera plus Tevimbra and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared to the control arm, trastuzumab plus chemotherapy.
- Ziihera plus Tevimbra and chemotherapy also demonstrated clinically meaningful and statistically significant improvements in overall survival (OS), and Ziihera plus chemotherapy demonstrated a clinically meaningful effect with a strong trend toward statistical significance for OS compared to the control arm at the time of this first analysis. The trial is ongoing with an additional planned OS interim analysis for Ziihera plus chemotherapy currently expected in mid-2026.
- A PFS and OS benefit was observed in the Ziihera plus Tevimbra and chemotherapy arm versus the control arm in both PD-L1 positive and PD-L1 negative subgroups.
- Both Ziihera plus Tevimbra and chemotherapy, and Ziihera plus chemotherapy demonstrated improvements in the key secondary endpoints of objective response rate (ORR) and duration of response (DoR) versus the control arm and these endpoints were supportive of the primary efficacy endpoints.
The safety profile of Ziihera in combination with chemotherapy, with or without Tevimbra, was generally consistent with the known safety profile of each agent with no new safety signals observed in the two investigational combination arms, and supports the overall benefit-risk of Ziihera for use in this indication.
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Jazz plans to submit these data for presentation at a major medical meeting in the first quarter of 2026 and for publication in a peer-reviewed journal, and will rapidly submit for adoption in the National Comprehensive Cancer Network Guidelines (NCCN Guidelines).
“The topline results from HERIZON-GEA-01 represent a true turning point for patients with HER2+ gastroesophageal adenocarcinoma, marking real progress in an indication that has historically had limited treatment options and poor outcomes,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “These data highlight the potential of zanidatamab to transform the standard of care in HER2+ indications, demonstrate the strength of our Azymetric™ platform to engineer novel and differentiated multifunctional biologics, and reinforce the strategic value of our partnership strategy with Jazz and BeOne in bringing this critical therapy to patients worldwide.”
Jazz expects to submit a supplemental Biologics License Application in the first half of 2026 to support Ziihera as a first-line treatment for patients with HER2+ locally advanced or metastatic GEA for use as part of a standard chemotherapy regimen with or without Tevimbra. Zanidatamab is currently approved in the U.S., Europe and China for use in second-line biliary tract cancer (BTC) and is marketed under the trade name, Ziihera, by Jazz and BeOne.
Zymeworks is eligible for additional regulatory and commercial milestones, as well as tiered royalties on net sales of Ziihera from Jazz and BeOne.
Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule.
The FDA granted Breakthrough Therapy designation for zanidatamab’s development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from the FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer.
The full U.S. Prescribing Information for ZIIHERA, including BOXED Warning, is available here.
About Zymeworks Inc.
Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat conditions such as cancer, inflammation, and autoimmune disease.
The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeOne Medicines Ltd. (formerly BeiGene, Ltd.) and Jazz Pharmaceuticals Ireland Limited, granting each exclusive rights to develop and commercialize zanidatamab in different territories.