BeOne Medicines Reports Longer-Term Survival Benefits for TEVIMBRA-Based Regimens in HER2-Positive Gastroesophageal Adenocarcinoma
BeOne Medicines Ltd., a global oncology company, has announced new long-term survival results from the planned second interim analysis (IA2) and final formal analysis of the Phase 3 HERIZON-GEA-01 clinical trial. The findings further support the potential of TEVIMBRA® (tislelizumab) in combination with ZIIHERA® (zanidatamab) and chemotherapy as a first-line treatment for patients with HER2-positive, locally advanced or metastatic gastroesophageal adenocarcinoma (GEA).
The updated results will be presented as a late-breaking abstract during a rapid oral session at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, under abstract number LBA79. The analysis provides additional evidence on the durability of the survival benefit associated with the TEVIMBRA-containing regimen and compares outcomes across the three treatment arms evaluated in the study.
The results are particularly relevant for patients with HER2-positive advanced GEA, an aggressive cancer that can be difficult to treat once it has spread beyond its original site. Although HER2-targeted therapies have expanded treatment options, long-term survival remains a significant clinical challenge. The HERIZON-GEA-01 findings indicate that combining immunotherapy, targeted therapy and chemotherapy may offer a meaningful treatment option for this patient population.
Longer follow-up reinforces the survival benefit
The latest analysis was conducted after a median follow-up of 35.3 months, representing an additional 9.4 months of follow-up compared with the first interim analysis. This extended observation period allowed investigators to assess whether the survival benefits previously reported with the experimental treatment regimens were maintained over time.
The study evaluated TEVIMBRA plus ZIIHERA and chemotherapy against ZIIHERA plus chemotherapy and trastuzumab plus chemotherapy. The formal overall survival (OS) comparisons followed a sequential testing approach. Investigators first compared ZIIHERA plus chemotherapy with trastuzumab plus chemotherapy and then assessed TEVIMBRA plus ZIIHERA and chemotherapy against ZIIHERA plus chemotherapy.
The results demonstrated sustained long-term survival with the TEVIMBRA-containing regimen compared with the trastuzumab-based control regimen. Median overall survival reached 27.0 months for patients receiving TEVIMBRA plus ZIIHERA and chemotherapy. The corresponding overall survival hazard ratio was 0.65, with a 95% confidence interval (CI) of 0.52 to 0.80.
This represented an improvement from the hazard ratio of 0.72 reported at the first interim analysis, providing further evidence of a sustained treatment benefit with longer follow-up. According to BeOne, the regimen is the only treatment for patients with HER2-positive GEA to demonstrate a median overall survival exceeding two years.
The median overall survival result is an important milestone in a disease setting where durable disease control remains difficult to achieve. It also highlights the potential value of combining different treatment mechanisms in a first-line regimen, particularly for patients whose disease requires both HER2-directed treatment and broader antitumor activity.
ZIIHERA plus chemotherapy meets the remaining primary endpoint
The final formal analysis also demonstrated a statistically significant overall survival improvement with ZIIHERA plus chemotherapy compared with trastuzumab plus chemotherapy.
Median overall survival was 22.9 months in the ZIIHERA plus chemotherapy arm, compared with 19.6 months in the trastuzumab plus chemotherapy arm. The treatment comparison produced a hazard ratio of 0.76, with a 95% CI of 0.62 to 0.93 and a p-value of 0.0088.
These results met the remaining primary endpoint of the HERIZON-GEA-01 study, supporting the clinical benefit of the ZIIHERA-based combination compared with the trastuzumab-based regimen.
The findings are significant because they establish an additional treatment option within HER2-positive advanced GEA. ZIIHERA, also known as zanidatamab, is a HER2-targeted bispecific antibody, while trastuzumab is an established HER2-directed therapy. The trial’s findings support the activity of the ZIIHERA-based regimen and provide a basis for evaluating the added contribution of TEVIMBRA in the combination.
Adding TEVIMBRA was associated with longer median overall survival
The analysis also examined the incremental benefit of adding TEVIMBRA to ZIIHERA plus chemotherapy.
Patients receiving TEVIMBRA, ZIIHERA and chemotherapy had a median overall survival of 27.0 months, compared with 22.9 months among those receiving ZIIHERA plus chemotherapy alone. This represented a four-month difference in median overall survival.
The comparison produced a hazard ratio of 0.81, with a 95% CI of 0.65 to 1.00. However, the difference did not reach statistical significance, with a p-value of 0.0502, in the context of an underpowered analysis.
The distinction is important when interpreting the findings. Although the numerical results favored the TEVIMBRA-containing regimen, the comparison did not establish a statistically significant overall survival advantage over ZIIHERA plus chemotherapy under the study’s analysis conditions. The results therefore support a favorable survival trend but should not be interpreted as definitive proof of superiority between these two experimental regimens.
A consistent trend toward improved overall survival was observed regardless of programmed death-ligand 1 (PD-L1) status. Among patients with a PD-L1 tumor area positivity (TAP) score below 1%, the overall survival hazard ratio was 0.76, with a 95% CI of 0.52 to 1.10. Among patients with a PD-L1 TAP score of 1% or higher, the hazard ratio was 0.77, with a 95% CI of 0.58 to 1.02.
Although these subgroup estimates favored the TEVIMBRA-containing combination, their confidence intervals included 1.0. The findings therefore indicate a consistent direction of effect across the analyzed PD-L1 groups rather than establishing a statistically significant benefit within each subgroup.
The results may be clinically relevant because PD-L1 expression can help characterize tumors and inform treatment decisions in some cancer settings. Observing a similar direction of effect across these groups supports further consideration of the combination’s activity across different PD-L1 expression levels, while the statistical limitations of the subgroup analyses remain important.
Three-year survival rates favor the TEVIMBRA-containing regimen
The extended follow-up also showed that the TEVIMBRA-containing combination had the highest estimated three-year overall survival rate among the three treatment groups.
At 36 months, the estimated overall survival rates were:
- 39.8% with TEVIMBRA plus ZIIHERA and chemotherapy.
- 31.5% with ZIIHERA plus chemotherapy.
- 22.9% with trastuzumab plus chemotherapy.
These findings indicate that a greater proportion of patients receiving the TEVIMBRA-containing regimen were estimated to be alive three years after treatment compared with patients in either of the other study arms.
The three-year survival estimate is an important measure of longer-term treatment outcomes in advanced GEA. While median overall survival reflects the time at which half of the patients in a study population have died, the 36-month estimate provides a complementary view of how many patients may achieve longer survival.
The difference between the 39.8% rate for the TEVIMBRA-based regimen and the 22.9% rate for trastuzumab plus chemotherapy highlights the longer-term survival pattern observed in the trial. However, the interpretation of differences between individual arms must take into account the trial’s statistical testing framework and the distinction between descriptive survival estimates and formally established treatment comparisons.
Progression-free survival results provide additional evidence
In addition to overall survival, the Phase 3 HERIZON-GEA-01 trial evaluated progression-free survival (PFS), which measures the time patients remain alive without their disease worsening.
TEVIMBRA plus ZIIHERA and chemotherapy significantly improved progression-free survival compared with trastuzumab plus chemotherapy. Median PFS was 12.7 months in the TEVIMBRA-containing arm, compared with 8.3 months in the trastuzumab-based control arm. The hazard ratio was 0.61, with a 95% CI of 0.50 to 0.76.
These results indicate a lower risk of disease progression or death in the TEVIMBRA-containing treatment group relative to the control arm. The PFS findings complement the overall survival results by showing a benefit in delaying disease progression alongside the longer-term survival outcomes.
The ZIIHERA plus chemotherapy arm also demonstrated improved progression-free survival compared with trastuzumab plus chemotherapy. Median PFS was 12.4 months for ZIIHERA plus chemotherapy, compared with 8.3 months for the trastuzumab-based regimen. The reported hazard ratio was 0.65, with a 95% CI of 0.50 to 0.76.
Taken together, the PFS results reinforce the clinical activity of the ZIIHERA-based combinations in HER2-positive advanced GEA. They also show that both experimental regimens outperformed the trastuzumab plus chemotherapy arm on this endpoint, with the TEVIMBRA-containing regimen reporting the longest median PFS.
The combination of PFS and OS findings provides a broader picture of treatment outcomes. While PFS reflects the ability to delay progression, OS captures survival regardless of the subsequent treatments patients may receive. Both endpoints are important when assessing the potential value of a first-line treatment for advanced cancer.
BeOne highlights the clinical significance of the findings
Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne, said the latest analysis provides additional evidence supporting the TEVIMBRA-based combination following its U.S. approval in August.
“Following the U.S. approval in August, these longer-term data provide further evidence supporting TEVIMBRA plus ZIIHERA and chemotherapy as the new standard of care in all first-line HER2-positive advanced gastroesophageal adenocarcinoma patients, regardless of PD-L1 status,” Lanasa said.
He added that the magnitude of the survival benefit previously demonstrated with TEVIMBRA plus ZIIHERA and chemotherapy compared with trastuzumab plus chemotherapy increased with longer follow-up. He also highlighted that nearly 40% of patients receiving the TEVIMBRA-containing regimen were alive at three years, describing this as a compelling result in a challenging disease area.
The comments reflect the company’s view that the updated findings strengthen the case for the regimen in first-line HER2-positive advanced GEA. The reported results also provide additional information on the durability of the treatment effect beyond the initial interim analysis.
The company announced the U.S. approval of the TEVIMBRA-based regimen in August 2026. The updated ESMO presentation is intended to provide clinicians and the oncology research community with more mature survival data from the pivotal trial.
Safety profile remains consistent with earlier findings
Safety results from both experimental treatment arms were generally consistent with those reported at the first interim analysis and with the known safety profiles of the component therapies. No new safety signals were identified in the updated analysis.
Diarrhea was the most common Grade 3 or higher treatment-related adverse event (TRAE). Because diarrhea was an important safety consideration during treatment, mandatory antidiarrheal prophylaxis was established during the first treatment cycle. Most diarrhea events occurred early in treatment.
The updated safety findings suggest that the longer follow-up did not reveal a new pattern of adverse events beyond what had been observed previously. Nevertheless, treatment decisions require careful consideration of the full safety profile of each combination, including the monitoring and management of adverse events associated with targeted therapy, immunotherapy and chemotherapy.
The early occurrence of many diarrhea events also highlights the importance of proactive monitoring and supportive care. Establishing prophylactic measures during the first cycle may help clinical teams manage this risk as patients begin treatment, although individual management decisions depend on patient characteristics and clinical judgment.
Implications for first-line HER2-positive advanced GEA
HER2-positive gastroesophageal adenocarcinoma represents a clinically important subgroup of advanced gastric and gastroesophageal cancers. Although HER2-directed therapies have become central to treatment for eligible patients, improving the duration of survival remains a major objective.
The HERIZON-GEA-01 results support the continued evaluation of combination approaches that bring together HER2 targeting, immune checkpoint inhibition and chemotherapy. The extended overall survival and progression-free survival findings provide additional evidence that the TEVIMBRA-containing regimen can deliver sustained clinical activity in the first-line setting.
The reported median overall survival of 27.0 months and estimated three-year survival rate of 39.8% are notable outcomes in this patient population. At the same time, the comparison between TEVIMBRA plus ZIIHERA and chemotherapy and ZIIHERA plus chemotherapy did not reach statistical significance for overall survival. That distinction remains essential when assessing the strength of the evidence for the incremental benefit of adding TEVIMBRA.
The results also demonstrate that ZIIHERA plus chemotherapy improved overall survival compared with trastuzumab plus chemotherapy, meeting the remaining primary endpoint of the study. This adds to the evidence supporting ZIIHERA-based treatment in HER2-positive advanced GEA.
The updated findings will be presented at the ESMO Congress 2026 in Madrid as late-breaking abstract LBA79. The presentation is expected to contribute to ongoing clinical discussions about first-line treatment selection, long-term outcomes and the role of combination therapies in HER2-positive advanced gastroesophageal adenocarcinoma.
Overall, the longer-term HERIZON-GEA-01 data reinforce the survival and disease-control benefits observed with TEVIMBRA plus ZIIHERA and chemotherapy compared with trastuzumab plus chemotherapy. They also confirm the overall survival benefit of ZIIHERA plus chemotherapy over the trastuzumab-based control regimen. These results provide further evidence for treatment strategies designed to extend survival in patients with HER2-positive locally advanced or metastatic GEA, while underscoring the importance of interpreting each comparison within the trial’s statistical framework.
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 evaluated dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
About ZIIHERA (zanidatamab-hrii)
ZIIHERA (zanidatamab-hrii) 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.1
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)
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 cornerstone 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 for various solid tumors (see prescribing information) in over 50 countries, and more than 2.2 million patients have been treated globally.