Announcement • Sep 01

Beone Medicines Announces Positive Topline Results from Second Interim Analysis of Phase 3 Herizon-Gea-01 Trial Evaluating Ziihera in Combination with Chemotherapy with and Without Tevimbra as First-Line Treatment for Her2+ Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma

BeOne Medicines Ltd. 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+ locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). At IA2, 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 the study. IA2 also provided longer follow-up data for the TEVIMBRA plus ZIIHERA and chemotherapy regimen, demonstrating an improved OS hazard ratio, continued durable outcomes, and a generally manageable safety profile. These results reinforce findings from IA1, in which the regimen met the progression-free survival (PFS) and OS endpoints, with the overall survival benefit observed across PD-L1 and HER2+ expression levels. On August 25, 2026, the U.S. Food and Drug Administration (FDA) approved supplemental Biologics License Applications (sBLAs) for both ZIIHERA and TEVIMBRA in combination with chemotherapy for the first-line treatment of adult patients with unresectable locally advanced or metastatic HER2+ 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. The approval was based on results from IA1 of HERIZON-GEA-01, which were published in The New England Journal of Medicine earlier this year. The safety profile of ZIIHERA plus chemotherapy and TEVIMBRA plus ZIIHERA and chemotherapy at IA2 was generally consistent with that of IA1 and the known safety profiles of the individual treatment components, with no new safety signals identified. The results from IA2 have been submitted for presentation at a major medical meeting in the fourth quarter of 2026. HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with Jazz Pharmaceuticals, to evaluate and compare the efficacy and safety of ZIIHERA plus chemotherapy, with and without TEVIMBRA, to the standard of care (trastuzumab plus chemotherapy) as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: ZIIHERA in combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial evaluated dual primary endpoints, PFS per blinded independent central review (BICR) and OS. ZIIHERA (zanidatamab) is a bispecific human epidermal growth factor receptor 2, or HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is approved in China for the treatment of patients who have unresectable, locally advanced, or metastatic HER2-high expression (IHC 3+) biliary tract cancer (BTC) and who have received prior systemic therapy. ZIIHERA has also been granted accelerated approval in the U.S. and conditional marketing authorization in the European Union for eligible BTC patients. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule. BeOne has licensed zanidatamab from Zymeworks in Asia (excluding India and Japan), Australia and New Zealand. Jazz Pharmaceuticals has rights in all other regions. ZIIHERA is a registered trademark of Zymeworks BC Inc. TEVIMBRA is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fc?) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. TEVIMBRA is the cornerstone of BeOne’s solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global TEVIMBRA clinical development program includes almost 15,000 patients enrolled to date in 30+ countries and regions across 71 trials, including 21 registration-enabling studies. TEVIMBRA is approved for various solid tumors (see prescribing information) in over 50 countries, and more than 2 million patients have been treated globally. Serious and sometimes fatal adverse reactions occurred with TEVIMBRA treatment. Warnings and Precautions include severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, and solid organ transplant rejection. Other warnings and precautions include infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity. The most common adverse reactions (=20%), including lab abnormalities, in patients receiving TEVIMBRA + zanidatamab + chemotherapy were diarrhea, nausea, anemia, decreased appetite, vomiting, hypokalemia, fatigue, rash, decreased neutrophil count, decreased platelet count, peripheral neuropathy, infusion-related reaction, and increased AST.

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Beone Medicines Announces Positive Topline Results from Second Interim Analysis of Phase 3 Herizon-Gea-01 Trial Evaluating Ziihera in Combination with Chemotherapy with and Without Tevimbra as First-Line Treatment for Her2+ Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma

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