CClinicalTrials.gg
RecruitingNCT06282575Updated Sep 14, 2026

Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

A Phase 3 interventional study of Zanidatamab and Cisplatin in Biliary Tract Cancer, sponsored by Jazz Pharmaceuticals. Recruiting at 185 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.

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

Phase
Phase 3
Study type
Interventional
Enrollment
286
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

02

Conditions studied

  • Biliary Tract Cancer

Keywords

  • JZP598
  • ZW25
  • HER-2 positive BIliary Tract cancer
  • Gallbladder Cancer
  • Intrahepatic Cholangiocarcinoma (ICC)
  • Extrahepatic Cholangiocarcinoma (ECC)
  • Zanidatamab
  • HER-2 overexpression
  • HER-2 amplification
03

Who can participate

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

Inclusion criteria

  1. Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
  2. Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
  3. Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
  4. HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
  5. Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
  6. Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  8. Adequate organ function
  9. Females of childbearing potential must have a negative pregnancy test result.
  10. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion criteria

Exclusion Criteria

  1. Prior treatment with a HER2-targeted agent
  2. Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
  3. The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
  4. Use of systemic corticosteroids.
  5. Brain metastases
  6. Severe chronic or active infections
  7. History of allogeneic organ transplantation.
  8. Active or prior autoimmune inflammatory conditions
  9. History of interstitial lung disease or non-infectious pneumonitis.
  10. Participation in another clinical trial with an investigational medicinal product within the last 3 months.
  11. Females who are breastfeeding
  12. Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
  13. Use of phenytoin
04

Study design

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

Study arms

  • Experimental
    Zanidatamab with Standard-of-care Therapy Arm

    Zanidatamab plus standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

    Drug: Zanidatamab · Drug: Cisplatin · Drug: Gemcitabine · Drug: Pembrolizumab · Drug: Durvalumab

  • Active comparator
    Standard-of-care Therapy Arm

    Standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

    Drug: Cisplatin · Drug: Gemcitabine · Drug: Pembrolizumab · Drug: Durvalumab

Interventions

  • DrugZanidatamab

    Administered intravenously (IV)

    Also known as: ZW25, JZP598, ZIIHERA®

  • DrugCisplatin

    Administered intravenously (IV)

  • DrugGemcitabine

    Administered intravenously (IV)

  • DrugPembrolizumab

    Administered intravenously (IV)

  • DrugDurvalumab

    Administered intravenously (IV)

05

What researchers measure

Primary outcomes

  1. Progression Free Survival (PFS) in participants with Immunohistochemistry (IHC) 3+ tumors

    PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.

    Time frame: Up to 52 months

Secondary outcomes

  1. Overall survival (OS) in participants with IHC 3+ tumors

    OS is defined as the time from randomization to death, due to any cause.

    Time frame: Up to 68 months

  2. Progression Free Survival for all participants

    PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.

    Time frame: Up to 68 months

  3. OS for all participants

    OS is defined as the time from randomization to death, due to any cause.

    Time frame: Up to 68 months

  4. Number of participants achieving Confirmed objective response rate (cORR)

    Confirmed objective response rate is defined as achieving a confirmed best overall response of Complete Response (CR) or Partial Response (PR)

    Time frame: Up to 68 months

  5. Duration of response (DOR)

    Duration of response is defined as the time from the first objective response (CR or PR) to documented Progressive Disease (PD) or death, from any cause.

    Time frame: Up to 68 months

  6. Number of Patients reporting Treatment-Emergent Adverse Events (TEAE)

    Time frame: Up to 68 months

  7. Maximum serum concentration of Zanidatamab

    Time frame: Up to 68 months

  8. Number of participants who develop Anti-drug antibodies (ADAs) to Zanidatamab

    Time frame: Up to 68 months

  9. Time to definitive deterioration (TDD) for participants with IHC 3+ tumors in patient-reported Physical Functioning (PF) domain score as measured by the EORTC QLQ-C30

    TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) final scores range from 0 to 100, where higher scores reflect better functioning

    Time frame: Up to 68 months

  10. TDD for all participants in patient-reported PF domain score as measured by the EORTC QLQ-C30

    TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-C30 final scores range from 0 to 100, where higher scores reflect better functioning.

    Time frame: Up to 68 months

  11. TDD for participants with IHC 3+ tumors in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain and Pruritis)

    TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer module (QLQ-BIL21) (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.

    Time frame: Up to 68 months

  12. TDD for all participants in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis)

    TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.

    Time frame: Up to 68 months

06

Study locations

73 of 185 sites recruiting
  • City of Hope(City of Hope National Medical Center, City of Hope Medical Center)
    Duarte, California 91010, United States
    Active, not recruiting
  • Rocky Mountain Cancer Centers, LLP
    Lone Tree, Colorado 80124, United States
    Withdrawn
  • AdventHealth Hematology and Oncology
    Orlando, Florida 32804, United States
    Recruiting
  • Winship Cancer Institute
    Atlanta, Georgia 30322, United States
    Completed
  • The University of Kansas Cancer Center - Westwood
    Westwood, Kansas 66205, United States
    Withdrawn
  • Norton Cancer Institute - Audubon
    Louisville, Kentucky 40217, United States
    Recruiting
  • Ochsner Clinic Foundation
    New Orleans, Louisiana 70121, United States
    Active, not recruiting
  • Tufts Medical Center
    Boston, Massachusetts 02111, United States
    Withdrawn
  • University of Michigan Hospital
    Ann Arbor, Michigan 48109, United States
    Completed
  • Henry Ford Health System
    Detroit, Michigan 48202, United States
    Withdrawn
  • Minnesota Oncology Hematology, P.A.
    Maple Grove, Minnesota 55369, United States
    Withdrawn
  • Atlantic Health System/Morristown Medical Center
    Morristown, New Jersey 07960, United States
    Withdrawn
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone - Ambulatory Care Center
    New York, New York 10016, United States
    Completed
  • Memorial Sloan Kettering Cancer Centers
    New York, New York 10022, United States
    Recruiting
  • Oregon Health and Science University
    Portland, Oregon 97239, United States
    Recruiting
  • Saint Francis Cancer Center
    Greenville, South Carolina 29607, United States
    Withdrawn
  • SCRI Oncology Partners
    Nashville, Tennessee 37203, United States
    Withdrawn
  • Texas Oncology - DFW
    Dallas, Texas 75246, United States
    Withdrawn
  • University of Texas Southwestern Medical Center
    Dallas, Texas 75390, United States
    Completed
  • The Univerrsity of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
    Active, not recruiting
  • Virginia Commonwealth University, VCU Health
    Richmond, Virginia 23219, United States
    Recruiting
  • Hospital Italiano de Buenos Aires
    Ciudad Autónoma de Buenos Aires (caba), Buenos Altes C1199ABB, Argentina
    Active, not recruiting
  • Fundación ARS Médica
    San Salvador de Jujuy, Jujuy Province 4600, Argentina
    Completed
  • Centro de Investigaciónes Clínicas - Clínica Viedma
    Viedma, Río Negro Province R8500ACE, Argentina
    Active, not recruiting
  • Hospital Provincial Del Centenario
    Rosario, Santa Fe Province 2000, Argentina
    Completed
  • Instituto Médico de la Fundación Estudios Clínicos
    Rosario, Santa Fe Province S2013DTC, Argentina
    Recruiting
  • CAIPO Centro para la Atención Integral del Paciente Oncológico
    San Miguel de Tucumán, Tucumán Province 4000, Argentina
    Active, not recruiting
  • Centro Médico en Oncología Clínica EXELSUS S.R.L
    San Miguel de Tucumán, Tucumán Province 4000, Argentina
    Recruiting
  • Centro Médico Privado CEMAIC
    Córdoba, X5008HHW, Argentina
    Completed
  • Imelda VZW
    Bonheiden, Antwerpen 2820, Belgium
    Recruiting
  • UZ Antwerpen
    Edegem, Antwerpen 2650, Belgium
    Recruiting
  • UZ Leuven
    Leuven, Vlaams-Brabant 3000, Belgium
    Active, not recruiting
  • Liga Norte Riograndense Contra O Cancer
    Natal, Rio Grande do Norte 59062-000, Brazil
    Active, not recruiting
  • Hospital de Clinicas de Porto Alegre - HCPA
    Porto Alegre, Rio Grande do Sul 90035-903, Brazil
    Completed
  • Irmandade Da Santa Casa de Misericordia de Porto Alegre - ISCMPA
    Porto Alegrev, Rio Grande do Sul 90020-170, Brazil
    Active, not recruiting
  • Fundação Pio XII Hospital de Amor de Barretos
    Barretos, São Paulo 14.784-400, Brazil
    Active, not recruiting
  • Fundação Doutor Amaral Carvalho - Hospital Amaral Carvalho
    Jaú, São Paulo 17210-080, Brazil
    Active, not recruiting
  • Fundação Faculdade Regional de Medicina de São José do Rio Preto (FUNFARME)
    São José do Rio Preto, São Paulo 15090-000, Brazil
    Active, not recruiting
  • Hospital Nossa Senhora Da Conceição/Centro Integrado de Pesquisa em Oncologia CIPO-GHC
    Porto Alegre, 91350-200, Brazil
    Recruiting
  • Instituto Nacional de Cancer - INCA
    Rio de Janeiro, 20230-130, Brazil
    Active, not recruiting
  • London Health Sciences Centre
    London, Ontario NGA 5W9, Canada
    Active, not recruiting
  • Princess Margaret Cancer Centre - University Health Network
    Toronto, Ontario M5G 2M9, Canada
    Recruiting
  • Centre Hospitalier de l'Universite de Montreal (CHUM)
    Montreal, Quebec H2X 0C1, Canada
    Active, not recruiting
  • James Lind Centro de Investigacion del Cancer
    Temuco, Araucania 4800827, Chile
    Recruiting
  • Servicios Médicos URUMED SpA
    Rancagua, Libertador Gen Bernardo O Higgins 2820000, Chile
    Completed
  • Clinica Puerto Montt
    Port Montt, Los Lagos Region 5507642, Chile
    Completed
  • Centro de Investigacion y Especialidades Medicas (CDIEM)
    Santiago, Santiago Metropolitan 7500859, Chile
    Recruiting
  • Fundación Arturo López Pérez (FALP)
    Santiago, Santiago Metropolitan 7500921, Chile
    Recruiting
  • Oncovida
    Santiago, Santiago Metropolitan 7500994, Chile
    Recruiting
  • Biocinetic Ltda
    Santiago, Santiago Metropolitan 8320000, Chile
    Recruiting
  • Hospital Clinico Universidad de Chile
    Santiago, Santiago Metropolitan 8380494, Chile
    Recruiting
  • The First Affiliated Hospital of USTC(Anhui Provincial Hospital)
    Hefei, Anhui 230036, China
    Recruiting
  • Beijing Cancer Hospital
    Beijing, Beijing Municipality 100142, China
    Recruiting
  • The First Hospital of Lanzhou University
    Lanzhou, Gansu 730000, China
    Recruiting
  • Harbin Medical University Cancer Hospital
    Harbin, Heilongjiang 150086, China
    Recruiting
  • Hunan Provincial People's Hospital
    Changsha, Hunan 410016, China
    Completed
  • Jilin Cancer Hospital
    Changchun, Jilin 130000, China
    Recruiting
  • Shandong Provincial Third Hospital
    Jinan, Shandong 250000, China
    Completed
  • Sichuan Cancer Hospital
    Chengdu, Sichuan 610041, China
    Completed
  • West China Hospital Sichuan University
    Chengdu, Sichuan 610041, China
    Recruiting
  • Zhongshan Hospital Fudan University
    Shanghai, 200032, China
    Recruiting
  • Fakultní nemocnice Brno, Interní hematologická a onkologická klinika
    Brno, 625 00, Czechia
    Withdrawn
  • Fakultni nemocnice Hradec Kralove, Klinika onkologie a radioterapie
    Hradec Králové, 50005, Czechia
    Withdrawn
  • Fakultni nemocnice v Motole, Onkologicka klinika
    Prague, 150 00, Czechia
    Withdrawn
  • Docrates Cancer Center
    Helsinki, 180, Finland
    Recruiting
  • Comprehensive Cancer Center, Helsinki University Hospital
    Helsinki, 290, Finland
    Recruiting
  • Kuopio University Hospital
    Kuopio, 70029, Finland
    Recruiting
  • CHU de Toulouse- (Toulouse University Hospital Center)
    Toulouse, Cedex 9 31059, France
    Recruiting
  • CHU Besancon
    Besançon, Cedex 25030, France
    Withdrawn
  • CHU de Bordeaux - Hôpital Haut Leveque
    Pessac, Cedex 33604, France
    Recruiting
  • CHU Brest Hôpital de la Cavale Blanche
    Brest, 29200, France
    Active, not recruiting
  • CHU Estaing
    Clermont-Ferrand, 63100, France
    Active, not recruiting
  • Hospital Beaujon University
    Clichy, 92110, France
    Active, not recruiting
  • Hopital Henri Mondor
    Créteil, 94010, France
    Active, not recruiting
  • CHU Montepellier - Hôpital Saint Eloi
    Montpellier, 34000, France
    Completed
  • CHU Poitiers
    Poitiers, 86000, France
    Recruiting
  • Institut de Cancérologie de l'Ouest
    Saint-Herblain, 44805, France
    Completed
  • Gustave Roussy
    Villejuif, 94805, France
    Completed
  • Universitätsklinikum Freiburg - Klinik für Innere Medizin II,
    Freiburg im Breisgau, Baden-Wurttemberg 79106, Germany
    Completed
  • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
    Heidelberg, Baden-Wurttemberg 69120, Germany
    Completed
  • Universitätsklinikum Tübingen - Medizinische Universitätsklinik, Innere Medizin I
    Tübingen, Baden-Wuttemberg 72076, Germany
    Recruiting
  • LMU Universitätsklinikum München, Campus Großhadern, Medizinische Klinik und Poliklinik III - Hämatologie und Onkologie
    München, Bavaria 81377, Germany
    Active, not recruiting
  • Krankenhaus Nordwest - Institut für Klinisch-Onkologische Forschung (IFK)
    Frankfurt am Main, Hesse 60488, Germany
    Recruiting
  • Medizinische Hochschule Hannover - Klinik Fur Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
    Hanover, Nieder-Sachsen 30625, Germany
    Recruiting
  • Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus
    Dresden, Saxony 01307, Germany
    Recruiting
  • Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Medizinische Klinik I (MKI)
    Lübeck, Schleswig-Holstein 23562, Germany
    Recruiting
  • Charité - Universitätsmedizin Berlin - Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie und Tumorimmunologie
    Berlin, 13353, Germany
    Active, not recruiting
  • Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona - Onkologie und Palliativmedizin mit Sektionen Hamatologie und Rheumatologie
    Hamburg, 22763, Germany
    Recruiting
  • KLES Dr Prabhakar Kore Hospital and Medical Research Centre
    Belagavi, Karnataka 590010, India
    Active, not recruiting
  • Tata Memorial Hospital
    Mumbai, Maharashtra 4000012, India
    Recruiting
  • Chopda Medicare & Research Centre Pvt. Ltd - Magnum Heart Institute
    Nashik, Maharashtra 422005, India
    Completed
  • AIG Hospitals (A Unit of Asian Institute of Gastroenterology)
    Hyderabad, Telangana 500032, India
    Recruiting
  • Pi Health Cancer Hospital
    Hyderabad, Telangana 500032, India
    Recruiting
  • Mahamana Pandit Madan Mohan Malviya Cancer Centre
    Varanasi, Uttar Pradesh 221005, India
    Recruiting
  • Max Super Speciality Hospital - Saket (a unit of Devki Devi foundation)
    New Delhi, 110017, India
    Active, not recruiting
  • Rajiv Gandhi Cancer Institute And Research Centre
    New Delhi, 110085, India
    Completed
  • Rambam Health Care Campus
    Haifa, 3109601, Israel
    Active, not recruiting
  • The Hadassah University Medical Center, Ein Kerem Hospital
    Jerusalem, 91120, Israel
    Active, not recruiting
  • Rabin Medical Center, Bellinson Hospital
    Petah Tikva, 49100, Israel
    Completed
  • The Chaim Sheba Medical Center, Tel Hashomer
    Ramat Gan, HaMerkaz, 5265601, Israel
    Active, not recruiting

Showing the first 100 of 185 sites across 25 countries.

07

References and documents

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

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06282575
Lead sponsor
Jazz Pharmaceuticals
Responsible party
Sponsor
First posted
Feb 28, 2024
Start date
Jul 19, 2024
Primary completion
Dec 1, 2028 (estimated)
Completion
Apr 1, 2030 (estimated)
Last update
Sep 14, 2026

Study contacts

Clinical Trial Disclosure & Transparency
Contact
ClinicalTrialDisclosure@JazzPharma.com
215-832-3750

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
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