BeOne Medicines Receives FDA Approval for TEVIMBRA Combination in First-Line HER2-Positive Gastroesophageal Cancer
BeOne Medicines Ltd., a global oncology-focused biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental Biologics License Application (sBLA) for TEVIMBRA® (tislelizumab) in combination with ZIIHERA® (zanidatamab) and chemotherapy for the first-line treatment of adults with unresectable, locally advanced or metastatic HER2-positive (HER2+) gastric, gastroesophageal junction, or esophageal adenocarcinoma (GEA).
The approval marks an important development in the treatment of HER2-positive gastroesophageal adenocarcinoma, a difficult-to-treat group of cancers associated with significant morbidity and mortality. The decision expands the treatment options available to patients in the United States and further establishes TEVIMBRA as an important component of BeOne Medicines’ oncology portfolio.
The FDA approval is supported by results from the global Phase 3 HERIZON-GEA-01 clinical trial, which evaluated the combination of TEVIMBRA, ZIIHERA and chemotherapy in patients receiving first-line treatment for advanced or metastatic HER2-positive GEA. Results from the study were published earlier this year in The New England Journal of Medicine and presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Addressing an Unmet Need in Gastroesophageal Cancer
Gastroesophageal adenocarcinoma encompasses cancers originating in the stomach, gastroesophageal junction and esophagus. Despite improvements in diagnosis and treatment, advanced and metastatic forms of the disease continue to present major challenges for patients and physicians.
More than 31,000 new stomach cancer cases are diagnosed annually in the United States, while approximately 20% of patients with gastroesophageal adenocarcinoma are estimated to have HER2-positive disease. HER2, or human epidermal growth factor receptor 2, is a protein that can promote the growth and spread of cancer cells when it is present at elevated levels.
HER2-positive gastroesophageal cancer has historically been challenging to manage, particularly once the disease becomes unresectable, locally advanced or metastatic. Although treatment advances have improved outcomes for some patients, long-term survival remains limited.
In the United States, fewer than 40% of patients with advanced or metastatic HER2-positive GEA survive beyond two years. These statistics illustrate the continuing need for new first-line treatment approaches capable of extending survival and controlling disease progression.
The newly approved regimen combines three components with complementary treatment approaches: TEVIMBRA, an immunotherapy, ZIIHERA, a HER2-targeted therapy, and chemotherapy. The strategy is intended to address the disease through multiple mechanisms and provide patients with an intensive treatment approach from the beginning of therapy.
HERIZON-GEA-01 Trial Supports FDA Decision
The FDA approval is based on results from HERIZON-GEA-01, a global Phase 3 randomized clinical trial evaluating the efficacy and safety of ZIIHERA plus chemotherapy, with or without TEVIMBRA, compared with trastuzumab plus chemotherapy.
The study specifically evaluated first-line treatment in patients with advanced or metastatic HER2-positive gastroesophageal adenocarcinoma. The results demonstrated statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) for patients treated with the TEVIMBRA, ZIIHERA and chemotherapy combination.
One of the most notable findings was the improvement in overall survival. Patients receiving the TEVIMBRA-based combination achieved a median overall survival of 26.4 months, compared with 19.2 months for patients in the control arm.
This represents a difference of more than seven months in median overall survival and demonstrates the potential of the combination to extend the time patients live following treatment initiation.
The trial also showed a meaningful improvement in progression-free survival. Median PFS was 12.4 months for patients receiving TEVIMBRA plus ZIIHERA and chemotherapy, compared with 8.1 months in the control group.
Progression-free survival measures the length of time patients live without their cancer worsening. The improvement in this endpoint provides additional evidence that the combination can delay disease progression compared with the established control regimen.
Benefits Observed Across PD-L1 Subgroups
Another important aspect of the HERIZON-GEA-01 results was the consistency of treatment benefit across patients with different levels of PD-L1 expression.
PD-L1 is a biomarker commonly evaluated in cancer treatment and can be used to help characterize tumors and, in certain settings, guide therapeutic decisions. In HERIZON-GEA-01, improvements in overall survival and progression-free survival were observed across PD-L1 subgroups.
The treatment demonstrated particularly notable results among patients with PD-L1-negative tumors, defined in the study as a tumor area positivity (TAP) score below 1%.
Among these patients, median overall survival reached 29.7 months with TEVIMBRA plus ZIIHERA and chemotherapy, compared with 15.8 months in the control arm.
The observation of benefit regardless of PD-L1 status could be clinically significant because it suggests that physicians may have greater flexibility when considering this regimen for eligible patients. The FDA approval does not require selection based on PD-L1 status for the approved indication, according to the company.
Jaffer A. Ajani, M.D., Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, described first-line treatment as a critical opportunity to influence the course of advanced HER2-positive gastroesophageal adenocarcinoma.
He emphasized the importance of providing effective treatment combinations at the beginning of care and noted that the median overall survival of more than two years observed with the regimen represents meaningful progress in a disease where improving long-term outcomes has historically been difficult.
Efficacy Across HER2 Expression Levels
The HERIZON-GEA-01 results also showed efficacy across different levels of HER2 expression.
The TEVIMBRA, ZIIHERA and chemotherapy combination demonstrated benefit in both HER2 IHC 3+ and HER2 IHC 2+ patient populations. Immunohistochemistry, or IHC, is a laboratory testing method used to determine the level of specific proteins expressed in tumor tissue.
The ability to demonstrate efficacy across these HER2 expression groups could broaden the relevance of the treatment combination for patients with HER2-positive gastroesophageal adenocarcinoma.
Because HER2 expression can vary among tumors, demonstrating consistent activity across different levels may be important when physicians evaluate treatment strategies for individual patients.
Safety Profile Remained Consistent
In addition to efficacy, safety is a critical consideration when evaluating a combination regimen that includes immunotherapy, targeted therapy and chemotherapy.
According to BeOne Medicines, treatment with TEVIMBRA plus ZIIHERA and chemotherapy was generally consistent with the known safety profiles of the individual components. The company reported that no new safety signals were identified in the study.
The safety findings provide additional support for the FDA-approved regimen, although patients receiving the combination will continue to require appropriate monitoring for adverse reactions associated with the individual therapies and chemotherapy.
The overall benefit-risk profile will remain an important consideration for physicians as they determine whether the treatment is appropriate for individual patients.
Expanding the Role of TEVIMBRA in Oncology
For BeOne Medicines, the FDA decision represents another important milestone in the development and commercialization of TEVIMBRA.
Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne Medicines, described the approval as an important achievement for the company and its efforts to expand the impact of TEVIMBRA across cancer types.
TEVIMBRA is one of the company’s key oncology assets, and the new indication further demonstrates BeOne Medicines’ strategy of developing combination regimens intended to address difficult-to-treat cancers.
The company views TEVIMBRA as a foundational asset within its solid tumor portfolio. Its combination with ZIIHERA and chemotherapy illustrates BeOne Medicines’ broader approach of investigating immunotherapy alongside targeted therapies and established treatment modalities.
The company said the approval reinforces its commitment to developing innovative and potentially practice-changing treatment combinations for patients with significant unmet medical needs.
Patient and Caregiver Perspective
The approval also carries significance for patients and families affected by HER2-positive gastroesophageal cancer.
Aki Smith, Founder and Executive Director of Hope for Stomach Cancer, highlighted the importance of additional treatment options for patients and caregivers confronting the disease.
For families facing advanced gastroesophageal cancer, improvements in survival can provide opportunities for additional time with loved ones and greater confidence that treatment options are continuing to evolve. Smith also emphasized the importance of helping patients and caregivers understand available therapies and obtain appropriate support throughout their treatment journey.
The availability of another first-line treatment option could therefore provide patients and healthcare professionals with an additional tool when developing individualized treatment plans.
Potential Impact on First-Line Treatment
First-line treatment is particularly important in advanced or metastatic cancer because it represents the initial systemic therapy administered after the disease reaches a stage where surgery or localized treatment is not sufficient.
The HERIZON-GEA-01 results suggest that combining immune-based therapy with HER2-directed treatment and chemotherapy can produce substantial improvements in disease control and survival compared with the control regimen.
The median overall survival of 26.4 months reported with the TEVIMBRA-based combination is particularly notable given the historically poor prognosis associated with advanced HER2-positive GEA.
The results also suggest that treatment benefits extend across important biological subgroups, including different PD-L1 statuses and HER2 expression levels.
The FDA approval of TEVIMBRA in combination with ZIIHERA and chemotherapy provides a new first-line treatment option for adults with unresectable, locally advanced or metastatic HER2-positive gastric, gastroesophageal junction or esophageal adenocarcinoma in the United States.
Supported by the Phase 3 HERIZON-GEA-01 trial, the approval is based on improvements in both overall survival and progression-free survival. Patients receiving the combination achieved median overall survival of 26.4 months versus 19.2 months with the control regimen, while median progression-free survival was 12.4 months compared with 8.1 months.
The observed benefits across PD-L1 subgroups, including patients with PD-L1-negative tumors, and across HER2 IHC 3+ and IHC 2+ populations further strengthen the clinical significance of the findings.
For BeOne Medicines, the decision expands the reach of TEVIMBRA and advances its broader strategy of developing combination therapies for patients with challenging cancers. For physicians and patients, the approval adds another option to the treatment landscape for HER2-positive gastroesophageal adenocarcinoma, where significant unmet medical needs remain.
As the new regimen becomes available in the United States, its clinical use will add to the growing range of targeted and immune-based approaches being evaluated for gastroesophageal cancers. The approval underscores continued progress in precision oncology and highlights the potential value of combining complementary treatment strategies to improve outcomes for patients facing advanced disease.
About the HERIZON-GEA-01 Phase 3 Trial
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 ZIIHERAplus 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: ZIIHERAin combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
About ZIIHERA (zanidatamab-hrii)
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.5
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.
About TEVIMBRA (tislelizumab-jsgr)
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 (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
TEVIMBRA is the foundational asset 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 in over 50 countries, and more than 2 million patients have been treated globally.
Select Important Safety Information
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, decreased neutrophil count, hypokalemia, fatigue, rash, decreased platelet count, peripheral neuropathy, infusion-related reaction, and increased aspartate aminotransferase.
About BeOne
BeOne Medicines is a global oncology company that is discovering and developing innovative treatments for cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. The Company has a growing global team spanning six continents who are driven by scientific excellence and exceptional speed to reach more patients than ever before.