CClinicalTrials.gg
Active, not recruitingNCT05152147HERIZON-GEA-01Updated Sep 24, 2026

A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

A Phase 3 interventional study of Zanidatamab and Tislelizumab in Gastric Neoplasms, Gastroesophageal Adenocarcinoma and Esophageal Adenocarcinoma, sponsored by Jazz Pharmaceuticals. Active, not recruiting at 227 sites in 33 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.

Sponsored by Jazz Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
920
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is being done to find out if zanidatamab, when given with chemotherapy plus or minus tislelizumab, is safe and works better than trastuzumab given with chemotherapy.

The patients in this study will have advanced human epidermal growth factor 2 (HER2)-positive stomach and esophageal cancers that are no longer treatable with surgery (unresectable) or chemoradiation, and/or have grown or spread to other parts of the body (metastatic).

02

Conditions studied

  • Gastric Neoplasms
  • Gastroesophageal Adenocarcinoma
  • Esophageal Adenocarcinoma

Keywords

  • HER2
  • Bispecific antibody
  • Biparatopic antibody
  • Immunotherapy
  • Gastric cancers
  • Esophageal cancers
  • Chemotherapy
  • FP
  • Capecitabine
  • Cisplatin
  • 5-FU
  • Oxaliplatin
  • Gastroesophageal adenocarcinoma
  • CAPOX
  • Programmed cell death receptor 1 (PD-1)
  • Anti-PD-1
  • Anti PD-1
  • JZP598
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (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. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment
  • Assessable (measurable or non-measurable) disease as defined by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization
  • Adequate organ function
  • Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)

Exclusion criteria

Exclusion Criteria:

  • Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unresectable locally advanced, recurrent or metastatic GEA
  • Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are completely off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization)
  • Known history of or ongoing leptomeningeal disease (LMD)
  • Known additional malignancy that is not considered cured or that has required treatment within the past 3 years
  • Known active hepatitis
  • Any history of human immunodeficiency virus (HIV) infection
  • Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible
  • QTc Fridericia (QTcF) > 470 ms
  • Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF)
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
920 participants (actual)

Study arms

  • Active comparator
    Arm A

    Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)

    Drug: Trastuzumab · Drug: Capecitabine · Drug: Oxaliplatin · Drug: Cisplatin · Drug: 5-Fluorouracil

  • Experimental
    Arm B

    Zanidatamab plus physician's choice of CAPOX or FP

    Drug: Zanidatamab · Drug: Capecitabine · Drug: Oxaliplatin · Drug: Cisplatin · Drug: 5-Fluorouracil

  • Experimental
    Arm C

    Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP

    Drug: Zanidatamab · Drug: Tislelizumab · Drug: Capecitabine · Drug: Oxaliplatin · Drug: Cisplatin · Drug: 5-Fluorouracil

Interventions

  • DrugZanidatamab

    Administered IV

    Also known as: ZW25, JZP598, ZIIHERA®

  • DrugTislelizumab

    Administered IV

  • DrugTrastuzumab

    Administered intravenously (IV)

    Also known as: Herceptin®

  • DrugCapecitabine

    Administered orally (PO bid)

  • DrugOxaliplatin

    Administered IV

  • DrugCisplatin

    Administered IV

  • Drug5-Fluorouracil

    Administered IV

05

What researchers measure

Primary outcomes

  1. Progression-free survival (PFS) by BICR

    The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) as assessed by blinded independent central review (BICR) or death from any cause

    Time frame: Up to 2.5 years

  2. Overall survival

    The time from randomization to death due to any cause

    Time frame: Up to 3.5 years

Secondary outcomes

  1. Confirmed objective response rate (ORR) by BICR

    Number of patients who achieved a best overall response of complete response (CR) or (PR) as determined per RECIST 1.1 as assessed by BICR

    Time frame: Up to 2.5 years

  2. Duration of response (DOR) by BICR

    The time from the first objective response (CR or PR) per BICR to documented progressive disease per RECIST 1.1 as assessed by BICR or death from any cause

    Time frame: Up to 2.5 years

  3. PFS per Investigator assessment

    The time from randomization to the date of documented disease progression (per RECIST 1.1) as assessed by Investigator or death from any cause

    Time frame: Up to 2.5 years

  4. Confirmed ORR per Investigator assessment

    Number of patients who achieved a best overall response of CR or PR as determined per RECIST 1.1 as assessed by Investigator

    Time frame: Up to 2.5 years

  5. DOR per Investigator assessment

    The time from the first objective response (CR or PR) per Investigator to documented progressive disease per RECIST 1.1 as assessed by Investigator or death from any cause

    Time frame: Up to 2.5 years

  6. Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR

    The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) as assessed by blinded independent central review (BICR) or death from any cause

    Time frame: Up to 2.5 years

  7. Assessment of Contribution of Components based on Overall Survival

    The time from randomization to death due to any cause

    Time frame: Up to 3.5 years

  8. Incidence of adverse events

    Number of subjects who experienced adverse events or serious adverse events

    Time frame: Up to 2 years

  9. Incidence of clinical laboratory abnormalities

    Number of patients who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

    Time frame: Up to 2 years

  10. Health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (core cancer questionnaire) C30 (QLQ-C30)

    Changes from baseline in the EORTC QLQ-C30 scores

    Time frame: Up to 2.5 years

  11. HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25)

    Changes from baseline in the EORTC QLQ-OG25 scores

    Time frame: Up to 2.5 years

  12. HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire

    Changes from baseline in the EORTC EQ-5D-5L questionnaire scores

    Time frame: Up to 2.5 years

  13. Serum concentration of zanidatamab and tislelizumab

    Time frame: Up to 2 years

  14. Incidence of anti-drug antibodies (ADAs)

    Number of patients who develop ADAs

    Time frame: Up to 2 years

06

Study locations

227 sites
  • Hospital de Gastroenterología Dr Bonorino Udaondo
    Buenos Aires, 1264, Argentina
  • Instituto de Investigaciones Metabólicas - IDIM
    Buenos Aires, C1012, Argentina
  • Hospital Italiano de Buenos Aires
    Buenos Aires, C1181ACH, Argentina
  • Fundación Centro de Medicina Nuclear y Molecular ER
    Córdoba, X5000HXL, Argentina
  • Centro Médico Privado CEMAIC
    Córdoba, X5008HHW, Argentina
  • Centro de Investigación Pergamino S.A.
    Pergamino, 2700, Argentina
  • Centro de Investigación Clínica - Clínica Viedma
    Viedma, R8500ACE, Argentina
  • Flinders Medical Centre
    Bedford Park, 5042, Australia
  • Austin Health
    Heidelberg, 3084, Australia
  • Liverpool Hospital
    Liverpool, 2170, Australia
  • Fiona Stanley Hospital
    Murdoch, 6150, Australia
  • Imelda VZW
    Bonheiden, 2820, Belgium
  • Cliniques Universitaires Saint-Luc
    Brussels, 1200, Belgium
  • UZ Gent
    Ghent, 9000, Belgium
  • UZ Leuven
    Leuven, 3000, Belgium
  • CHU de Liège
    Liège, 4000, Belgium
  • Centro Integrado de Pesquisa - CIP
    Barretos, 14784-400, Brazil
  • Fundação Pio XII Hospital de Câncer de Barretos
    Barretos, 14784-400, Brazil
  • Cenantron - Centro Avancado de Tratamento Oncologico Ltda
    Belo Horizonte, 30130-090, Brazil
  • Centro de Pesquisas Clínicas/Fundação Doutor Amaral Carvalho
    Brasília, 70840-901, Brazil
  • Instituto Do Câncer Do Ceará ICC
    Fortaleza, 60430-230, Brazil
  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
    Porto Alegre, 90050-170, Brazil
  • Irmandade Da Santa Casa de Misericordia de Porto Alegre
    Porto Alegre, 90050-170, Brazil
  • Hospital Nossa Senhora Da Conceição
    Porto Alegre, 91350-200, Brazil
  • Núcleo de Pesquisa Clínica da Rede São Camilo
    Santo André, 09060-650, Brazil
  • Instituto do Cancer do Estado de São Paulo ICESP
    São Paulo, 01246-000, Brazil
  • Instituto de Oncologia de Sorocaba
    Sorocaba, 18030-075, Brazil
  • Princess Margaret Cancer Centre
    Toronto, M5G 2C1, Canada
  • Centro Internacional de Estudios Clinicos CIEC
    Santiago, Region Metropolitan 8420383, Chile
  • Fundación Arturo López Pérez (FALP) - PPDS
    Providencia, Santiago Metropolitan 7500000, Chile
  • Centro de Estudios Clínicos SAGA SpA
    Providencia, 7500000, Chile
  • Sociedad Oncovida S.A
    Santiago, 7500000, Chile
  • Icegclinic
    Santiago, 8150513, Chile
  • BIOCINETIC SpA
    Santiago, 8330336, Chile
  • Sociedad de Investigaciones Medicas Limitada
    Temuco, 4810469, Chile
  • Beijing Chao-Yang Hospital, Capital Medical University
    Beijing, 100020, China
  • Cancer Hospital Chinese Academy of Medical Sciences
    Beijing, 100021, China
  • Beijing Cancer Hospital
    Beijing, 100142, China
  • Peking University Third Hospital
    Beijing, 100191, China
  • Beijing Luhe Hospital, Capital Medical University
    Beijing, 101199, China
  • The First Affiliated Hospital of Bengbu Medical College
    Bengbu, 233004, China
  • Hunan Cancer Hospital
    Changsha, 410031, China
  • Changzhi People's Hospital
    Changzhi, 046099, China
  • Changzhou First People's Hospital
    Changzhou, 213004, China
  • Sichuan Cancer Hospital & Institute
    Chengdu, 610042, China
  • The First Affiliated Hospital of Fujian Medical University
    Fuzhou, 350005, China
  • Fujian Cancer Hospital
    Fuzhou, 350014, China
  • Guangdong Provincial People's Hospital
    Guangzhou, 510055, China
  • The Sixth Affiliated Hospital of Sun Yat-sen University
    Guangzhou, 510655, China
  • Hainan General Hospital
    Haikou, 570311, China
  • The First Affiliated Hospital, College of Medicine, Zhejiang University
    Hangzhou, 310003, China
  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    Hangzhou, 310016, China
  • Second Affiliated Hospital of Zhejiang University School of Medicine
    Hangzhou, 310017, China
  • Zhejiang Cancer Hospital
    Hangzhou, 310022, China
  • Harbin Medical University Cancer Hospital
    Harbin, 150081, China
  • Anhui Provincial Cancer Hospital
    Hefei, 230031, China
  • The Second Affiliated Hospital of Anhui Medical University
    Hefei, 230601, China
  • Affiliated Hospital of Inner Mongolia Medical University
    Hohhot, 01000, China
  • Shandong Cancer Hospital
    Jinan, 250000, China
  • Jinan Central Hospital
    Jinan, 250013, China
  • Yunnan Cancer Hospital
    Kunming, 650118, China
  • The First Hospital of Lanzhou University
    Lanzhou, 730013, China
  • Gansu Cancer Hospital
    Lanzhou, 730050, China
  • The First Affiliated Hospital of Nanchang University
    Nanchang, 330052, China
  • Nanjing Drum Tower Hospital ,The Affiliated Hospital of Nanjing University Medical School
    Nanjing, 210008, China
  • The Affiliated Hospital of Qingdao University
    Qingdao, 266003, China
  • Ruijin hospital Shanghai Jiao Tong University School of Medicine
    Shanghai, 200025, China
  • Fudan University Affiliated Zhongshan Hospital
    Shanghai, 200032, China
  • Fudan University Shanghai Cancer Center
    Shanghai, 200032, China
  • Shanghai General Hospital
    Shanghai, 200080, China
  • Liaoning Cancer Hospital & Institute
    Shenyang, 110801, China
  • The Fourth Hospital of Hebei Medical University
    Shijiazhuang, 50011, China
  • Tianjin Medical University General Hospital
    Tianjin, 300041, China
  • Tianjin Medical University Cancer Institute & Hospital
    Tianjin, 300060, China
  • The Tonghua Central Hospital
    Tonghua, 143099, China
  • Cancer Hospital affiliated to Xinjiang Medical University
    Ürümqi, 830026, China
  • Weihai Municipal Hospital
    Weihai, 264200, China
  • The First Affiliated Hospital of Wenzhou Medical University
    Wenzhou, 325000, China
  • Union Hospital Tongji Medical College HuaZhong University of Science and Technology
    Wuhan, 430023, China
  • Hubei Cancer Hospital
    Wuhan, 430079, China
  • Affiliated Hospital of Jiangnan University
    Wuxi, 214062, China
  • First Affiliated Hospital of Xi 'an Jiaotong University
    Xi'an, 710061, China
  • The First Affiliated Hospital of Xiamen University
    Xiamen, 361003, China
  • Northern Jiangsu People's Hospital
    Yangzhou, 225001, China
  • Henan Cancer Hospital
    Zhengzhou, 450003, China
  • The First Affiliated Hospital of Zhengzhou University
    Zhengzhou, 450052, China
  • North Estonia Medical Centre Foundation
    Tallinn, 13419, Estonia
  • CHU de Bordeaux - Hopital Haut Leveque
    Pessac, Gironde 33600, France
  • Sainte-Catherine, Institut du Cancer Avignon Provence
    Avignon, 84000, France
  • EDOG - Institut Bergonie - PPDS
    Bordeaux, 33000, France
  • Universite de Bourgogne - Faculte de Medecine - IN
    Dijon, 21079, France
  • Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
    Grenoble, 38043, France
  • Centre Léon Berard
    Lyon, 69008, France
  • EDOG Institut de Cancerologie de l'Ouest - PPDS
    Nantes, 44805, France
  • CHRU de Poitiers La Miletrie
    Poitiers, 86021, France
  • EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
    Rennes, 35000, France
  • CHRU de Brest - Hopital Morvan
    Saint-Priest-en-Jarez, 42270, France
  • Hôpital de Rangueil
    Toulouse, 69437, France
  • Hôpital Saint Antoine
    Villejuif, 94800, France
  • Research Institute of Clinical Medicine
    Tbilisi, 0112, Georgia

Showing the first 100 of 227 sites across 33 countries.

07

References and documents

Publications

  • Shitara K, Elimova E, Liu T, Tabernero J, Lee KW, Schenker M, Tebbutt NC, Ajani J, Salimin N, Ku G, Gwang Kim J, Ales Diaz I, Zhang J, Pietrantonio F, Bai LY, Le Sourd S, Zhao J, Hierro C, Kiberu A, Van Herpe F, Bao Y, Zhang H, Yang L, Li V, Gartner EM, Chen Y, Grim J, Rha SY, Shen L; HERIZON-GEA-01 Investigators. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer. N Engl J Med. 2026 May 28;394(20):2002-2014. doi: 10.1056/NEJMoa2517729. PubMed 42202319 ↗
  • Lee KW, Bai LY, Jung M, Ying J, Im YH, Oh DY, Cho JY, Oh SC, Chao Y, Kim JW, Chen Y, Li V, Chen S, Kang YK. Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2026 Jan 16;32(2):312-323. doi: 10.1158/1078-0432.CCR-24-4295. PubMed 41324998 ↗
  • Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036. PubMed 40341124 ↗
  • Tabernero J, Shen L, Elimova E, Ku G, Liu T, Shitara K, Lin X, Boyken L, Li H, Grim J, Ajani J. HERIZON-GEA-01: Zanidatamab + chemo +/- tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Future Oncol. 2022 Sep;18(29):3255-3266. doi: 10.2217/fon-2022-0595. Epub 2022 Aug 24. PubMed 36000541 ↗

Individual participant data

Plan to share: Yes — In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com.

08

Registry details

Key details

Study ID
NCT05152147
Lead sponsor
Jazz Pharmaceuticals
Collaborators
BeOne Medicines LTD, BeOne Pharmaceutical Co., Ltd.
Responsible party
Sponsor
First posted
Dec 9, 2021
Start date
Dec 2, 2021
Primary completion
Jul 15, 2026
Completion
Sep 30, 2027 (estimated)
Last update
Sep 24, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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