A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers
HERIZON-BTC-01
A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
2 other identifiers
interventional
87
9 countries
67
Brief 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), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2020
Typical duration for phase_2
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 6, 2020
CompletedFirst Posted
Study publicly available on registry
July 10, 2020
CompletedStudy Start
First participant enrolled
October 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 11, 2024
CompletedResults Posted
Study results publicly available
August 21, 2024
CompletedSeptember 15, 2025
August 1, 2025
2.8 years
July 6, 2020
July 28, 2024
August 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Up to 34 months
Secondary Outcomes (15)
Duration of Response (DOR) by ICR
Up to 45 months
DOR ≥ 16 Weeks by ICR
24 weeks, up to 45 months
Disease Control Rate (DCR) by ICR
Up to 45 months
Progression-free Survival (PFS) by ICR
Up to 45 months
ORR by Investigator Assessment
Up to 45 months
- +10 more secondary outcomes
Study Arms (1)
ZW25 (Zanidatamab) Monotherapy
EXPERIMENTALInterventions
Administered intravenously
Eligibility Criteria
You may qualify if:
- 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%.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jazz Pharmaceuticalslead
- BeiGenecollaborator
- Jazz Pharmaceuticals Ireland Limitedcollaborator
- BeOne Medicines LTDcollaborator
Study Sites (67)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
University of Arizona Cancer Center
Tucson, Arizona, 95724, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
University of California Los Angeles
Santa Monica, California, 90404, United States
The Oncology Institute of Hope and Innovation
Whittier, California, 90603, United States
Advent Health Cancer Institute
Orlando, Florida, 32804, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Texas Southwestern Medical Center - Hospital
Dallas, Texas, 75390, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Centro de Cáncer Nuestra Señora de la Esperanza
Santiago, 8330032, Chile
Radiomed (Clinica Alemana de Temuco)
Temuco, 645, Chile
Beijing Cancer Hospital
Beijing, 100142, China
Peking Union Medical College Hospital
Beijing, 100730, China
Jilin Cancer Hospital
Changchun, 130012, China
Hunan Cancer Hospital
Changsha, 410013, China
West China Hospital
Chengdu, 610041, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, 510080, China
The First Affiliated Hospital of Zhejiang University
Hangzhou, 310003, China
Zhejiang Provincial People's Hospital
Hangzhou, 310014, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, 310016, China
Zhejiang Cancer Hospital
Hangzhou, 310022, China
Affiliated Tumor Hospital of Harbin Medical University
Harbin, 150081, China
Anhui Provincial Hospital
Hefei, 230001, China
Huzhou Central Hospital
Huzhou, 313000, China
Jinhua Central Hospital
Jinhua, 321000, China
The First Hospital Of Lanzhou University
Lanzhou, 730000, China
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
Nanjing, 210008, China
Shandong Provincial Third Hospital
Shandong, 250031, China
Affiliated Zhongshan Hospital of Fudan University
Shanghai, 200032, China
The Third Affiliated Hospital of the Chinese PLA
Shanghai, 200081, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, 300060, China
Weifang People's Hospital
Weifang, 261000, China
Hubei Cancer Hospital
Wuhan, 430079, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, 450052, China
Oncologie médicale Hopital Jean Minjoz
Besançon, 25030, France
Institut de Cancerologie et d'Hematologie Hopital Morvan - CHRU de Brest
Brest, 29200, France
Hopitaux de La Timone
Marseille, 13385, France
Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie
Poitiers, 86000, France
Département De Médecine
Villejuif, 94805, France
Fondazione del Piemonte per l'Oncologia (IRCCS)
Candiolo, 10060, Italy
Istituto Clinico Humanitas
Milan, 20089, Italy
Istituto Nazionale Dei Tumori
Milan, 20133, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
Padua, 35128, Italy
Gyeongsang National University Hospital
Jinju, 52727, South Korea
Pusan National University Hospital
Pusan, 49241, South Korea
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center Hospital
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591, South Korea
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Universitario Germans Trias i Pujol
Barcelona, 08916, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital Universitario Doce de Octubre
Madrid, 28041, Spain
Corporacio Sanitaria Parc Tauli
Sabadell, 08208, Spain
Hospital Miguel Servet
Zaragoza, 50009, Spain
University College London Hospitals (UCLH)
London, NW1 2PG, United Kingdom
Royal Free London NHS Foundation Trust
London, NW3 2QG, United Kingdom
Imperial College Healthcare NHS Trust
London, W12 0HS, United Kingdom
Related Publications (2)
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.
PMID: 39114870DERIVEDHarding 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.
PMID: 37276871DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure & Transparency
- Organization
- Jazz Pharmaceuticals Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
July 6, 2020
First Posted
July 10, 2020
Study Start
October 1, 2020
Primary Completion
July 28, 2023
Study Completion
July 11, 2024
Last Updated
September 15, 2025
Results First Posted
August 21, 2024
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
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.