BeOne Medicines Reports Sustained Survival Benefit with TEVIMBRA-ZIIHERA Combination in First-Line HER2+ Gastroesophageal Cancer

BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced new survival results from the planned second interim analysis (IA2) and final formal analysis of the Phase 3 HERIZON-GEA-01 trial, further confirming the benefit of TEVIMBRA^® (tislelizumab) plus ZIIHERA^® (zanidatamab) and chemotherapy as first-line treatment for patients with HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). The results will be presented today as a late-breaking abstract during a rapid oral session at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain (LBA79).

Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne, said:

“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. The magnitude of the survival benefit previously demonstrated with TEVIMBRA plus ZIIHERA and chemotherapy versus trastuzumab plus chemotherapy increased after longer follow-up, with nearly 40% of patients receiving the TEVIMBRA-containing regimen alive at three years, representing a compelling result in this challenging disease area.”

Longer follow-up reinforces benefit of TEVIMBRA in combination regimen

This new analysis was conducted after 35.3 months of follow-up, an additional 9.4 months since the first interim analysis. Formal overall survival (OS) comparisons were tested sequentially, first comparing ZIIHERA plus chemotherapy with trastuzumab plus chemotherapy and then comparing TEVIMBRA plus ZIIHERA and chemotherapy with ZIIHERA plus chemotherapy.

Key findings include:

• TEVIMBRA plus ZIIHERA and chemotherapy demonstrated sustained long-term survival versus trastuzumab plus chemotherapy. Median OS was 27.0 months, with an OS hazard ratio (HR) of 0.65 (95% CI: 0.52-0.80), improved from 0.72 at the first interim analysis. This regimen is the only treatment for patients with HER2+ GEA to show a median overall survival of more than two years.

• ZIIHERA plus chemotherapy significantly improved OS versus trastuzumab plus chemotherapy. Median OS was 22.9 months versus 19.6 months, respectively (HR 0.76; 95% CI: 0.62-0.93; P=0.0088), meeting the remaining primary endpoint of the study.

• Adding TEVIMBRA to ZIIHERA plus chemotherapy was associated with a four-month longer median OS at 27.0 months compared with ZIIHERA plus chemotherapy with 22.9 months (HR 0.81; 95% CI: 0.65-1.00). The difference did not reach statistical significance (P=0.0502) in the context of an underpowered analysis. A consistent trend toward improved OS was observed irrespective of PD-L1 status (PD-L1 TAP<1% HR 0.76; 95% CI: 0.52-1.10; PD-L1 TAP≥1% HR 0.77; 95% CI: 0.58-1.02).

• Long-term survival was highest with the TEVIMBRA-containing regimen. Estimated 36-month OS was 39.8% with TEVIMBRA plus ZIIHERA and chemotherapy, 31.5% with ZIIHERA plus chemotherapy and 22.9% with trastuzumab plus chemotherapy.

• TEVIMBRA plus ZIIHERA and chemotherapy significantly improved progression-free survival (PFS) versus trastuzumab plus chemotherapy, with median PFS of 12.7 months versus 8.3 months (HR 0.61; 95% CI:0.5-0.76). Median PFS with ZIIHERA plus chemotherapy was 12.4 months versus trastuzumab plus chemotherapy (HR 0.65; 95% CI:0.5-0.76).

• The safety findings for both experimental arms were generally consistent with the first interim analysis, and with the known profiles of the component therapies. No new safety signals were identified, and diarrhea was the most common Grade ≥3 treatment-related adverse event (TRAE). A mandatory anti-diarrheal prophylaxis was established during the first cycle, with most diarrhea events occurring early in the treatment.

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.

Important Safety Information

The current European Summary of Product Characteristics (SmPC) for TEVIMBRA is available from the European Medicines Agency.

The information in this press release is intended for a global audience. Product indications vary by region.

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. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential of the HERIZON-GEA-01 regimens as a standard of care for first-line HER2-positive GEA; ongoing clinical development of zanidatamab and TEVIMBRA across multiple tumor types and disease settings; and BeOne’s plans, commitments, aspirations, and goals under the heading “About BeOne.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeOne's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law.

To access BeOne media resources, please visit ourNewsroomsite.

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¹ ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

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