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

NCT ID: NCT05152147

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

920 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-02

Study Completion Date

2027-07-31

Brief Summary

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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).

Detailed Description

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Conditions

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Gastric Neoplasms Gastroesophageal Adenocarcinoma Esophageal Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

multi-cohort, open-label, multicenter study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

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

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type DRUG

Administered intravenously (IV)

Capecitabine

Intervention Type DRUG

Administered orally (PO bid)

Oxaliplatin

Intervention Type DRUG

Administered IV

Cisplatin

Intervention Type DRUG

Administered IV

5-Fluorouracil

Intervention Type DRUG

Administered IV

Arm B

Zanidatamab plus physician's choice of CAPOX or FP

Group Type EXPERIMENTAL

Zanidatamab

Intervention Type DRUG

Administered IV

Capecitabine

Intervention Type DRUG

Administered orally (PO bid)

Oxaliplatin

Intervention Type DRUG

Administered IV

Cisplatin

Intervention Type DRUG

Administered IV

5-Fluorouracil

Intervention Type DRUG

Administered IV

Arm C

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

Group Type EXPERIMENTAL

Zanidatamab

Intervention Type DRUG

Administered IV

Tislelizumab

Intervention Type DRUG

Administered IV

Capecitabine

Intervention Type DRUG

Administered orally (PO bid)

Oxaliplatin

Intervention Type DRUG

Administered IV

Cisplatin

Intervention Type DRUG

Administered IV

5-Fluorouracil

Intervention Type DRUG

Administered IV

Interventions

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Zanidatamab

Administered IV

Intervention Type DRUG

Tislelizumab

Administered IV

Intervention Type DRUG

Trastuzumab

Administered intravenously (IV)

Intervention Type DRUG

Capecitabine

Administered orally (PO bid)

Intervention Type DRUG

Oxaliplatin

Administered IV

Intervention Type DRUG

Cisplatin

Administered IV

Intervention Type DRUG

5-Fluorouracil

Administered IV

Intervention Type DRUG

Other Intervention Names

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ZW25 JZP598 ZIIHERA® Herceptin®

Eligibility Criteria

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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

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeOne Medicines LTD

UNKNOWN

Sponsor Role collaborator

BeOne Pharmaceutical Co., Ltd.

UNKNOWN

Sponsor Role collaborator

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital de Gastroenterología Dr Bonorino Udaondo

Buenos Aires, , Argentina

Site Status

Instituto de Investigaciones Metabólicas - IDIM

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Site Status

Fundación Centro de Medicina Nuclear y Molecular ER

Córdoba, , Argentina

Site Status

Centro Médico Privado CEMAIC

Córdoba, , Argentina

Site Status

Centro de Investigación Pergamino S.A.

Pergamino, , Argentina

Site Status

Centro de Investigación Clínica - Clínica Viedma

Viedma, , Argentina

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Flinders Medical Centre

Bedford Park, , Australia

Site Status

Austin Health

Heidelberg, , Australia

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Liverpool Hospital

Liverpool, , Australia

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Fiona Stanley Hospital

Murdoch, , Australia

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Imelda VZW

Bonheiden, , Belgium

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Cliniques Universitaires Saint-Luc

Brussels, , Belgium

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UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

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CHU de Liège

Liège, , Belgium

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Centro Integrado de Pesquisa - CIP

Barretos, , Brazil

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Fundação Pio XII Hospital de Câncer de Barretos

Barretos, , Brazil

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Cenantron - Centro Avancado de Tratamento Oncologico Ltda

Belo Horizonte, , Brazil

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Centro de Pesquisas Clínicas/Fundação Doutor Amaral Carvalho

Brasília, , Brazil

Site Status

Instituto Do Câncer Do Ceará ICC

Fortaleza, , Brazil

Site Status

Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, , Brazil

Site Status

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Site Status

Hospital Nossa Senhora Da Conceição

Porto Alegre, , Brazil

Site Status

Núcleo de Pesquisa Clínica da Rede São Camilo

Santo André, , Brazil

Site Status

Instituto do Cancer do Estado de São Paulo ICESP

São Paulo, , Brazil

Site Status

Instituto de Oncologia de Sorocaba

Sorocaba, , Brazil

Site Status

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Centro Internacional de Estudios Clinicos CIEC

Santiago, Region Metropolitan, Chile

Site Status

Fundación Arturo López Pérez (FALP) - PPDS

Providencia, Santiago Metropolitan, Chile

Site Status

Centro de Estudios Clínicos SAGA SpA

Providencia, , Chile

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Sociedad Oncovida S.A

Santiago, , Chile

Site Status

Icegclinic

Santiago, , Chile

Site Status

BIOCINETIC SpA

Santiago, , Chile

Site Status

Sociedad de Investigaciones Medicas Limitada

Temuco, , Chile

Site Status

Beijing Chao-Yang Hospital, Capital Medical University

Beijing, , China

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Cancer Hospital Chinese Academy of Medical Sciences

Beijing, , China

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Beijing Cancer Hospital

Beijing, , China

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Peking University Third Hospital

Beijing, , China

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Beijing Luhe Hospital, Capital Medical University

Beijing, , China

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The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

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Hunan Cancer Hospital

Changsha, , China

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Changzhi People's Hospital

Changzhi, , China

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Changzhou First People's Hospital

Changzhou, , China

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Sichuan Cancer Hospital & Institute

Chengdu, , China

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The First Affiliated Hospital of Fujian Medical University

Fuzhou, , China

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Fujian Cancer Hospital

Fuzhou, , China

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Guangdong Provincial People's Hospital

Guangzhou, , China

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The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, , China

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Hainan General Hospital

Haikou, , China

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The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, , China

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Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, , China

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Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, , China

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Zhejiang Cancer Hospital

Hangzhou, , China

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Harbin Medical University Cancer Hospital

Harbin, , China

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Anhui Provincial Cancer Hospital

Hefei, , China

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The Second Affiliated Hospital of Anhui Medical University

Hefei, , China

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Affiliated Hospital of Inner Mongolia Medical University

Hohhot, , China

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Shandong Cancer Hospital

Jinan, , China

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Jinan Central Hospital

Jinan, , China

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Yunnan Cancer Hospital

Kunming, , China

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The First Hospital of Lanzhou University

Lanzhou, , China

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Gansu Cancer Hospital

Lanzhou, , China

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The First Affiliated Hospital of Nanchang University

Nanchang, , China

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Nanjing Drum Tower Hospital ,The Affiliated Hospital of Nanjing University Medical School

Nanjing, , China

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The Affiliated Hospital of Qingdao University

Qingdao, , China

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Ruijin hospital Shanghai Jiao Tong University School of Medicine

Shanghai, , China

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Fudan University Affiliated Zhongshan Hospital

Shanghai, , China

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Fudan University Shanghai Cancer Center

Shanghai, , China

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Shanghai General Hospital

Shanghai, , China

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Liaoning Cancer Hospital & Institute

Shenyang, , China

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The Fourth Hospital of Hebei Medical University

Shijiazhuang, , China

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Tianjin Medical University General Hospital

Tianjin, , China

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Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

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The Tonghua Central Hospital

Tonghua, , China

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Cancer Hospital affiliated to Xinjiang Medical University

Ürümqi, , China

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Weihai Municipal Hospital

Weihai, , China

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The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, , China

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Union Hospital Tongji Medical College HuaZhong University of Science and Technology

Wuhan, , China

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Hubei Cancer Hospital

Wuhan, , China

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Affiliated Hospital of Jiangnan University

Wuxi, , China

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First Affiliated Hospital of Xi 'an Jiaotong University

Xi'an, , China

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The First Affiliated Hospital of Xiamen University

Xiamen, , China

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Northern Jiangsu People's Hospital

Yangzhou, , China

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Henan Cancer Hospital

Zhengzhou, , China

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The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

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North Estonia Medical Centre Foundation

Tallinn, , Estonia

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CHU de Bordeaux - Hopital Haut Leveque

Pessac, Gironde, France

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Sainte-Catherine, Institut du Cancer Avignon Provence

Avignon, , France

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EDOG - Institut Bergonie - PPDS

Bordeaux, , France

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Universite de Bourgogne - Faculte de Medecine - IN

Dijon, , France

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Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon

Grenoble, , France

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Centre Léon Berard

Lyon, , France

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EDOG Institut de Cancerologie de l'Ouest - PPDS

Nantes, , France

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CHRU de Poitiers La Miletrie

Poitiers, , France

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EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS

Rennes, , France

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CHRU de Brest - Hopital Morvan

Saint-Priest-en-Jarez, , France

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Hôpital de Rangueil

Toulouse, , France

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Hôpital Saint Antoine

Villejuif, , France

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Research Institute of Clinical Medicine

Tbilisi, , Georgia

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High Technology Hospital MedCenter Ltd

Tbilisi, , Georgia

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Institut für Klinisch-Onkologische Forschung

Frankfurt am Main, Hesse, Germany

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Attikon University General Hospital

Athens, , Greece

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Bioclinic Thessaloniki Oncology Department

Thessaloniki, , Greece

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Agios Loucas Clinic SA

Thessaloniki, , Greece

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Interbalkan Medical Center of Thessaloniki Oncology Department

Thessaloniki, , Greece

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Clinica Medica Especializada CELAN

Guatemala City, , Guatemala

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Grupo Medico Angeles

Guatemala City, , Guatemala

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Centro Medico Integral de Cancerologia CEMIC

Salcajá, , Guatemala

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All India Institute of Medical Sciences, Bhubaneswar

Bhubaneswar, , India

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Artemis Hospital

Gūrgaon, , India

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MNJ Institute of Oncology and Regional Cancer Centre

Hyderabad, , India

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Indraprastha Apollo Hospitals

New Delhi, , India

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Regional Cancer Centre Indira Gandhi Institute of Medical Sciences

Patna, , India

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HCG City Cancer Center

Vijayawada, , India

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St James's Hospital

Dublin, , Ireland

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Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

Bologna, , Italy

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Fondazione del Piemonte per l'Oncologia (IRCCS)

Candiolo, , Italy

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Ospedale Policlinico San Martino

Genova, , Italy

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Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, , Italy

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Ospedale San Raffaele S.r.l. - PPDS

Milan, , Italy

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Istituto Nazionale Dei Tumori

Milan, , Italy

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ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda

Milan, , Italy

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Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, , Italy

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Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

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Fondazione Policlinico Universitario A Gemelli

Rome, , Italy

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Centro Ricerche Cliniche Di Verona

Verona, , Italy

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Azienda ULSS 8 "Berica" - Ospedale San Bortolo

Vicenza, , Italy

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Chiba Cancer Center

Chiba, Chiba, Japan

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National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

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Gifu University Hospital

Gifu, Gihu, Japan

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Gunma Prefectural Cancer Center

Ota-shi, Gunma, Japan

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Hyogo Cancer Center

Akashi-shi, Hyôgo, Japan

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Ibaraki Prefectural Central Hospital

Kasama-Shi, Ibaraki, Japan

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Kagawa University Hospital

Kita-Gun Miki-Cho, Kagawa-ken, Japan

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Kanagawa Cancer Center

Yokohama-Shi Asahi-Ku, Kanagawa, Japan

Site Status

Kumamoto University Hospital - Honjo-Kuhonji Campus A

Chuo-Ku, Kumamoto, Japan

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Kyoto University Hospital

Sakyo-ku, Kyoto-shi, Japan

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Osaki Citizen Hospital

Osaki-Shi, Miyagi, Japan

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Kurashiki Central Hospital

Kurashiki-Shi, Okayama-ken, Japan

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Osaka University Hospital

Suita-Shi, Osaka, Japan

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Osaka Medical and Pharmaceutical University Hospital

Takatsuki-Shi, Osaka, Japan

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Keio University Hospital

Shinjuku-Ku, Tokyo, Japan

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National Cancer Center Hospital

Chūōku, , Japan

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National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

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Saitama Cancer Center

Ina, , Japan

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Shikoku Cancer Center

Matsuyama, , Japan

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Osaka International Cancer Institute

Osaka, , Japan

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Kindai University Hospital

Ōsaka-sayama, , Japan

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The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, , Japan

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Hospital Pulau Pinang

George Town, , Malaysia

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Sarawak General Hospital

Kuching, , Malaysia

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National Cancer Institute ( Institut Kanser Negara)

Putrajaya, , Malaysia

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Health Pharma Professional Research S.A de C.V.

Mexico City, , Mexico

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Hospital Universitario Dr. Jose Eleuterio González

Monterrey, , Mexico

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Centro de Investigacion Clinica de Oaxaca

Oaxaca City, , Mexico

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Catharina Hospital

Eindhoven, , Netherlands

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Leids Universitair Medisch Centrum

Leiden, , Netherlands

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ETZ-Elisabeth

Tilburg, , Netherlands

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Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, , Poland

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Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie

Warsaw, , Poland

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Hospital Garcia de Orta

Almada, , Portugal

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Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, , Portugal

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Hospital Senhora da Oliveira - Guimaraes, E.P.E

Guimarães, , Portugal

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Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisbon, , Portugal

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Unidade Local de Saúde de Matosinhos SA

Matosinhos Municipality, , Portugal

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Centro Hospitalar do Porto EPE

Porto, , Portugal

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Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, , Portugal

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Fundeni Clinical Institute

Bucharest, , Romania

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Prof Dr I Chiricuta Institute of Oncology - PPDS

Cluj-Napoca, , Romania

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Medisprof SRL

Cluj-Napoca, , Romania

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Oncology Center Sfantul Nectarie

Craiova, , Romania

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University Clinical Center of Serbia - PPDS

Belgrade, , Serbia

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Clinical Hospital Center Bezanijska Kosa

Belgrade, , Serbia

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Oncology Institute of Vojvodina

Kamenitz, , Serbia

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University Clinical Center Nis

Niš, , Serbia

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National Cancer Center Singapore

Singapore, , Singapore

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Wilgers Oncology Centre

Pretoria, , South Africa

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Hallym University Sacred Heart Hospital

Anyang-si, , South Korea

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Dong-A University Hospital

Busan, , South Korea

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Kyungpook National University Chilgok Hospital

Daegu, , South Korea

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National Cancer Center

Goyang-si, , South Korea

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Gachon University Gil Medical Center

Incheon, , South Korea

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CHA Bundang Medical Center, CHA University

Seongnam-si, , South Korea

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Seoul National University Bundang Hospital

Seongnam-si, , South Korea

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Korea University Anam Hospital

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

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Kangbuk Samsung Hospital

Seoul, , South Korea

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Severance Hospital Yonsei University Health System - PPDS

Seoul, , South Korea

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Asan Medical Center

Seoul, , South Korea

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Gangnam Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Korea University Guro Hospital

Seoul, , South Korea

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Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

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Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

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Hospital Universitario Germans Trias i Pujol

Badalona, , Spain

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Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

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Hospital Universitari de Girona Dr Josep Trueta

Girona, , Spain

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Institut Català d'Oncologia (Hospital Duran y Reynals)

L'Hospitalet de Llobregat, , Spain

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Hospital Universitario Ramon y Cajal

Madrid, , Spain

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Hospital Universitario La Paz - PPDS

Madrid, , Spain

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Hospital Regional Universitario de Malaga - Hospital General

Málaga, , Spain

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Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, , Spain

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Hospital Universitario Marques de Valdecilla

Santander, , Spain

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Hospital Universitario Virgen Macarena

Seville, , Spain

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Hospital Universitario Miguel Servet

Zaragoza, , Spain

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China Medical University Hospital

Taichung, , Taiwan

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Taipei Veterans General Hospital

Taipei, , Taiwan

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Songklanagarind Hospital

Hat Yai, , Thailand

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Srinagarind Hospital, Khon Kaen University

Khon Kaen, , Thailand

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Hacettepe Universitesi Kanser Enstitusu

Ankara, , Turkey (Türkiye)

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Trakya University Medical Faculty

Edirne, , Turkey (Türkiye)

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Dokuz Eylul Universitesi

Izmir, , Turkey (Türkiye)

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Acibadem Adana Hospital

Seyhan, , Turkey (Türkiye)

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Medical Park Trabzon Yildizli

Trabzon, , Turkey (Türkiye)

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Dr. Abdurrahman Yurtaslan Ankara Onkology Training and Research Hospital

Yenimahalle, , Turkey (Türkiye)

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The Municipal Enterprise Volyn Regional Medical Oncology Centre of the Volyn Regional Council

Lutsk, , Ukraine

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Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

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Western General Hospital Edinburgh - PPDS

Edinburgh, , United Kingdom

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St James University Hospital

Leeds, , United Kingdom

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Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, , United Kingdom

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Royal Marsden Hospital - London

London, , United Kingdom

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Royal Marsden Hospital - Surrey

London, , United Kingdom

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Edith Cavell Hospital

Peterborough, , United Kingdom

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Weston Park Cancer Centre

Sheffield, , United Kingdom

Site Status

Countries

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Argentina Australia Belgium Brazil Canada Chile China Estonia France Georgia Germany Greece Guatemala India Ireland Italy Japan Malaysia Mexico Netherlands Poland Portugal Romania Serbia Singapore South Africa South Korea Spain Taiwan Thailand Turkey (Türkiye) Ukraine United Kingdom

References

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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 1b/2 Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2025 Dec 1. doi: 10.1158/1078-0432.CCR-24-4295. Online ahead of print.

Reference Type DERIVED
PMID: 41324998 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36000541 (View on PubMed)

Other Identifiers

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2021-000296-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

jRCT2061230026

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-510319-20-00

Identifier Type: CTIS

Identifier Source: secondary_id

ZWI-ZW25-301

Identifier Type: -

Identifier Source: org_study_id