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HER2-amplified Biliary Tract CancersPhase 2HERIZON-BTC-01NCT04466891

A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

A Phase 2 study testing ZW25 (Zanidatamab) in people with HER2-amplified Biliary Tract Cancers, run by Jazz Pharmaceuticals at 67 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2-amplified Biliary Tract Cancers
What is being tested?
ZW25 (Zanidatamab)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
67 sitesin 9 countries
Study dates
1 Oct 2020to 11 Jul 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC.
  • Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
  • Received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who received gemcitabine in prior adjuvant or neoadjuvant treatment, if progression occurred < 6 months from the latter of primary surgical resection or completion of gemcitabine-containing adjuvant therapy, they will be considered as having received 1 prior line of therapy for advanced disease.
  • Subjects must test positive for HER2 amplification by ISH-assay at a central laboratory on a new biopsy or archival tissue. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur at any time after diagnosis of advanced or metastatic disease and before study enrollment.
  • Male or female, ≥18 years of age (or the legal age of adulthood per country-specific regulations).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Adequate organ function.
  • Adequate cardiac function, as defined by left ventricular ejection fraction ≥ 50%.

Who cannot join

  • Received systemic anti-cancer therapy within 3 weeks of the first dose of ZW25. Received radiotherapy within 2 weeks of the first dose of ZW25.
  • Prior treatment with HER2-targeted agents.
  • Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening).
  • Known leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the investigator, the subject must be free of neurological symptoms of LMD.
  • Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, infected biloma or abscess. Any complications must be resolved more than 2 weeks prior to the first dose of ZW25.
  • Prior or concurrent malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Show all 11Show fewer
  • Active hepatitis
  • Infection with human immunodeficiency virus (HIV)-1 or HIV-2
  • QTc Fridericia (QTcF) > 470 ms.
  • History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease.
  • Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.

Trial locations and contacts

67 sites in 9 countries.

67 sites in 9 countries

China23 sites

  • Beijing Cancer Hospital

    Beijing, 100142

  • Peking Union Medical College Hospital

    Beijing, 100730

  • Jilin Cancer Hospital

    Changchun, 130012

  • Hunan Cancer Hospital

    Changsha, 410013

  • West China Hospital

    Chengdu, 610041

  • The First Affiliated Hospital, Sun Yat-sen University

    Guangzhou, 510080

  • The First Affiliated Hospital of Zhejiang University

    Hangzhou, 310003

  • Zhejiang Provincial People's Hospital

    Hangzhou, 310014

  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

    Hangzhou, 310016

  • Zhejiang Cancer Hospital

    Hangzhou, 310022

  • Affiliated Tumor Hospital of Harbin Medical University

    Harbin, 150081

  • Anhui Provincial Hospital

    Hefei, 230001

  • Huzhou Central Hospital

    Huzhou, 313000

  • Jinhua Central Hospital

    Jinhua, 321000

  • The First Hospital Of Lanzhou University

    Lanzhou, 730000

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

    Nanjing, 210008

  • Shandong Provincial Third Hospital

    Shandong, 250031

  • Affiliated Zhongshan Hospital of Fudan University

    Shanghai, 200032

  • The Third Affiliated Hospital of the Chinese PLA

    Shanghai, 200081

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, 300060

  • Weifang People's Hospital

    Weifang, 261000

  • Hubei Cancer Hospital

    Wuhan, 430079

  • The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, 450052

Other trials in China

United States14 sites

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • University of Texas Southwestern Medical Center - Hospital

    Dallas, Texas, 75390

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Advent Health Cancer Institute

    Orlando, Florida, 32804

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of California Los Angeles

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Arizona Cancer Center

    Tucson, Arizona, 95724

  • The Oncology Institute of Hope and Innovation

    Whittier, California, 90603

Other trials in United States

South Korea8 sites

  • Gyeongsang National University Hospital

    Jinju, 52727

  • Pusan National University Hospital

    Pusan, 49241

  • Seoul National University Bundang Hospital

    Seongnam, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center Hospital

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

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

    Seoul, 06591

Other trials in South Korea

Spain7 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Universitario Germans Trias i Pujol

    Barcelona, 08916

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Universitario Doce de Octubre

    Madrid, 28041

  • Corporacio Sanitaria Parc Tauli

    Sabadell, 08208

  • Hospital Miguel Servet

    Zaragoza, 50009

Other trials in Spain

France5 sites

  • Oncologie médicale Hopital Jean Minjoz

    Besançon, 25030

  • Institut de Cancerologie et d'Hematologie Hopital Morvan - CHRU de Brest

    Brest, 29200

  • Hopitaux de La Timone

    Marseille, 13385

  • Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie

    Poitiers, 86000

  • Département De Médecine

    Villejuif, 94805

Other trials in France

Italy4 sites

  • Fondazione del Piemonte per l'Oncologia (IRCCS)

    Candiolo, 10060

  • Istituto Clinico Humanitas

    Milan, 20089

  • Istituto Nazionale Dei Tumori

    Milan, 20133

  • Istituto Oncologico Veneto - I.R.C.C.S.

    Padova, 35128

Other trials in Italy

United Kingdom3 sites

  • University College London Hospitals (UCLH)

    London, NW1 2PG

  • Royal Free London NHS Foundation Trust

    London, NW3 2QG

  • Imperial College Healthcare NHS Trust

    London, W12 0HS

Other trials in United Kingdom

Chile2 sites

  • Centro de Cáncer Nuestra Señora de la Esperanza

    Santiago, 8330032

  • Radiomed (Clinica Alemana de Temuco)

    Temuco, 645

Other trials in Chile

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers

This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).

Being tested
ZW25 (Zanidatamab)
Keywords
HER2, Bispecific antibody, Biparatopic antibody, Immunotherapy, Biliary Tract Cancer, Intra-hepatic cholangiocarcinoma, Extra-hepatic cholangiocarcinoma, Gallbladder cancer, JZP598
Medical subject headings
Biliary Tract Neoplasms, Gallbladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZW25 (Zanidatamab)Drug

    Also called JZP598, ZW25, ZIIHERA®

    Administered intravenously

Study groups in NCT04466891
Study groupRoleWhat they receive
ZW25 (Zanidatamab) MonotherapyExperimentalNot described
Receives: Drug: ZW25 (Zanidatamab)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)

    Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.

    Measured: Up to 34 months

Secondary outcomes (15)

  1. Duration of Response (DOR) by ICR

    The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause

    Measured: Up to 45 months

  2. DOR ≥ 16 Weeks by ICR

    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

    Measured: 24 weeks, up to 45 months

  3. Disease Control Rate (DCR) by ICR

    Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1

    Measured: Up to 45 months

  4. Progression-free Survival (PFS) by ICR

    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause

    Measured: Up to 45 months

  5. ORR by Investigator Assessment

    Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1

    Measured: Up to 45 months

  6. DOR by Investigator Assessment

    The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause

    Measured: Up to 45 months

  7. DOR ≥ 16 Weeks by Investigator Assessment

    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

    Measured: 24 weeks, up to 45 months

  8. DCR by Investigator Assessment

    Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1

    Measured: Up to 45 months

  9. PFS by Investigator Assessment

    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause

    Measured: Up to 45 months

  10. Overall Survival

    The time from the first dose of study treatment until the date of death from any cause

    Measured: Up to 45 months

  11. Incidence of Adverse Events (AEs)

    Number of subjects who experienced AEs or serious adverse events

    Measured: Up to 45 months

  12. Incidence of Laboratory Abnormalities

    Number of subjects 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

    Measured: Up to 45 months

  13. Maximum Serum Concentration of ZW25

    Measured: Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose

  14. Trough Concentration of ZW25

    Minimum observed serum concentration (trough)

    Measured: Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose

  15. Incidence of Anti-drug Antibodies (ADAs)

    Number of subjects who develop ADAs

    Measured: Up to 45 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2020
  2. Study start1 Oct 2020
  3. Primary completion28 Jul 2023
  4. Study completion11 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
single-arm, open-label, multi-cohort, multicenter study
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04466891
Sponsor's protocol ID
ZWI-ZW25-203
Other IDs
2020-000459-11
Acronym
HERIZON-BTC-01
Status last verified
Aug 2025
First submitted
6 Jul 2020
Last updated
15 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.
Expanded access
Available

Publications

  • Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, Bao L, Sun HC, Macarulla T, Xie F, Metges JP, Ying J, Bridgewater J, Lee MA, Tejani MA, Chen EY, Kim DU, Wasan H, Ducreux M, Bao Y, Lindsey S, Bachini M, Morement H, Boyken L, Ma J, Garfin P, Pant S; HERIZON-BTC-01 study group. A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer. Future Oncol. 2024;20(31):2319-2329. doi: 10.1080/14796694.2024.2368952. Epub 2024 Aug 8.

    PubMed 39114870

  • Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, Bao L, Sun HC, Macarulla T, Xie F, Metges JP, Ying J, Bridgewater J, Lee MA, Tejani MA, Chen EY, Kim DU, Wasan H, Ducreux M, Bao Y, Boyken L, Ma J, Garfin P, Pant S; HERIZON-BTC-01 study group. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023 Jul;24(7):772-782. doi: 10.1016/S1470-2045(23)00242-5. Epub 2023 Jun 2.

    PubMed 37276871

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZW25 (Zanidatamab) in people with HER2-amplified Biliary Tract Cancers, run by Jazz Pharmaceuticals at 67 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in China, United States, South Korea, Spain, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR) (time frame: Up to 34 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04466891, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.

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