ZIIHERA Plus TEVIMBRA and Chemotherapy: A Potential New Standard for First-Line HER2+ Advanced GEA

BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced full results from the Phase 3 HERIZON-GEA-01 trial evaluating ZIIHERA^® (zanidatamab), a HER2-targeted bispecific antibody, in combination with chemotherapy, with and without PD-1 inhibitor TEVIMBRA^® (tislelizumab), as a first-line treatment for HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). These data, including the first interim overall survival (OS) analysis, will be presented as a Late-Breaking Abstract Oral Presentation (#LBA285) at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) on January 8, 2026, from 8:57- 9:07 a.m. PST.

HERIZON-GEA-01 met the dual primary endpoint of progression-free survival (PFS), demonstrating statistically significant and clinically meaningful improvements in both experimental arms compared to the control arm. The addition of TEVIMBRA to ZIIHERA and chemotherapy also showed a statistically significant and clinically meaningful improvement in overall survival (OS) (mOS: 26.4 months, HR=0.72 [95% CI: 0.57, 0.90]; P=0.0043), resulting in a 28% reduction in the risk of death and a greater than 7-month improvement in mOS. These PFS and OS benefits were observed in the ZIIHERA plus TEVIMBRA and chemotherapy arm versus the control arm regardless of PD-L1 expression level, with approximately one-third of enrolled patients with tumors classified as PD-L1 < 1%. ZIIHERA plus chemotherapy showed a clinically meaningful survival benefit with a mOS of 24.4 months, a strong trend toward statistical significance at the time of this first interim analysis for OS.

“The HERIZON-GEA-01 results are encouraging, with median overall survival for tislelizumab plus zanidatamab and chemotherapy surpassing two years, an outcome that marks a significant advancement in the treatment of metastatic HER2+ gastroesophageal adenocarcinoma,” said Manish Shah, M.D., Chief of the Solid Tumor Service and Director of Gastrointestinal Oncology at Weill Cornell Medicine and a medical oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, who serves as a paid advisory board member for Jazz Pharmaceuticals, Inc. and BeOne Medicines Ltd. “Unlike prior studies in HER2+ GEA with checkpoint blockade therapy, the addition of tislelizumab demonstrated meaningful activity even in TAP PD-L1 < 1%, suggesting a potential new treatment option for this subgroup, while broadening choices for patients with PD-L1 ≥1%.”

Further highlights from the HERIZON-GEA-01 results include:

• TEVIMBRA added to ZIIHERA and chemotherapy (n=302; mPFS: 12.4 months, HR=0.63 [95% CI: 0.51, 0.78], P=<0.0001) resulted in a 37% reduction in the risk of disease progression and a greater than 4-month improvement in mPFS.
• Patients receiving ZIIHERA plus chemotherapy (n=304; mPFS: 12.4 months, HR=0.65 [95% CI: 0.52, 0.81], P=<0.0001) showed a 35% reduction in the risk of disease progression and a similar greater than 4-month improvement in mPFS.
• These results compare favorably to mPFS of 8.1 months in patients treated with trastuzumab plus chemotherapy.
• In the PD-L1 negative subgroup (TAP score <1%), the HR results for PFS were 0.47 [95% CI: 0.32, 0.69] in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.49 [95% CI: 0.33, 0.73].
• In the PD-L1 positive subgroup (TAP score >1%), the HR results for PFS were 0.65 [95% CI: 0.49, 0.86] in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.82 [95% CI: 0.60, 1.10].
• Both experimental arms demonstrated improvements in the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) versus the control arm, with ZIIHERA and chemotherapy resulting in an ORR of 69.6% with a median DOR of 14.32 months (CI 95%: 11.53, 21.85). The ZIIHERA plus TEVIMBRA and chemotherapy arm induced an ORR of 70.7%, with the median DOR reaching 20.70 months (CI 95%: 12.55, 37.65), highlighting TEVIMBRA’s essential role in the durability of response observed with the regimen.

“The comprehensive results of the HERIZON-GEA-01 study, particularly the improvement in overall survival shown in the TEVIMBRA plus ZIIHERA and chemotherapy arm, pave the way for the adoption of a new standard in first-line HER2-positive metastatic GEA,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne. “BeOne holds commercial rights for ZIIHERA in most of Asia Pacific, where the GEA burden is highest. With these data, we anticipate the opportunity to expand access so more patients can benefit.”

The safety profile of ZIIHERA in combination with chemotherapy, with or without TEVIMBRA, was consistent with the known effects of HER2-directed therapy and immunotherapy, and no new safety signals were identified. Duration of treatment was longest on the ZIIHERA plus TEVIMBRA and chemotherapy arm. Rates of Grade ≥3 treatment-related adverse events (TRAEs) were 71.8% with ZIIHERA plus TEVIMBRA and chemotherapy, 59.0% with ZIIHERA plus chemotherapy, and 59.6% with trastuzumab plus chemotherapy. Rates of discontinuation of ZIIHERA or trastuzumab due to TRAEs were 11.9% with ZIIHERA plus TEVIMBRA and chemotherapy, 8.5% with ZIIHERA plus chemotherapy, and 2.3% in the trastuzumab plus chemotherapy arm. The most common Grade ≥3 treatment-related adverse event (TRAE) was diarrhea (24.5% of patients with ZIIHERA plus TEVIMBRA and chemotherapy; 20.0% with ZIIHERA plus chemotherapy; and 12.9% of patients in the trastuzumab plus chemotherapy arm). Importantly, discontinuation of either ZIIHERA or trastuzumab due to treatment-related diarrhea was uncommon (4.1% of patients with ZIIHERA plus TEVIMBRA and chemotherapy, 1.3% with ZIIHERA plus chemotherapy, and 0% of patients in the trastuzumab plus chemotherapy arm). Treatment-emergent diarrhea generally occurred early in treatment and resolved within 3 weeks. The manageable safety profile supports the feasibility of these combinations in the first-line metastatic setting.

These results will be submitted for publication in a peer-reviewed journal. BeOne intends to submit supplemental Biologics License Applications to the U.S. FDA for TEVIMBRA and to the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for TEVIMBRA and ZIIHERA, based on these data. The company also intends to work with authorities in its licensed territories to expedite regulatory submissions in these markets.

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 or 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. Appropriate 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 Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA), which includes cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide. Approximately 20% of GEA patients have HER2-positive disease^1,2,3, which has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 30% for gastric cancer and about 19% for GEA.⁴

About ZIIHERA (zanidatamab)
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 also has been approved in both the U.S. and 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 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 14,000 patients enrolled to date in 35 countries and regions across 70 trials, including 22 registration-enabling studies. TEVIMBRA is approved in at least one indication in 48 markets, and more than 1.8 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, dermatologic adverse reactions, nephritis with renal dysfunction, and solid organ transplant rejection. Other warnings and precautions include infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Please see fullU.S. Prescribing Informationincluding theU.S. Medication Guide.

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

About BeOne Medicines
BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more accessible to 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. With a growing global team of nearly 12,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. 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 benefits of ZIIHERA and TEVIMBRA; the potential of TEVIMBRA plus ZIIHERA and chemotherapy to become a new standard in first-line HER2-positive metastatic GEA; the potential opportunity to expand access; BeOne’s plans to expand TEVIMBRA’s label; BeOne’s expectations regarding ZIIHERA’s and TEVIMBRA’s clinical development and regulatory milestones; BeOne’s plans to submit the data for publication; and BeOne’s plans, commitments, aspirations, and goals under the heading “About BeOne Medicines.” 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.

¹ Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.
² Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.
³ Stroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249.
⁴ Battaglin F, et al. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell International. 2018;18(99).
⁵ ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.).

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