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

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).

Study Overview

• Status: Completed
• Conditions: HER2-amplified Biliary Tract Cancers
• Intervention / Treatment: Drug: ZW25 (Zanidatamab)

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• Chile
  • Santiago, Chile, 8330032
    • Centro de Cáncer Nuestra Señora de la Esperanza
  • Temuco, Chile, 645
    • Radiomed (Clinica Alemana de Temuco)
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Changchun, China, 130012
    • Jilin Cancer Hospital
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Chengdu, China, 610041
    • West China Hospital
  • Guangzhou, China, 510080
    • The First Affiliated Hospital, Sun Yat-sen University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of Zhejiang University
  • Hangzhou, China, 310014
    • Zhejiang Provincial People's Hospital
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Harbin, China, 150081
    • Affiliated Tumor Hospital of Harbin Medical University
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Huzhou, China, 313000
    • Huzhou Central Hospital
  • Jinhua, China, 321000
    • Jinhua Central Hospital
  • Lanzhou, China, 730000
    • The First Hospital of Lanzhou University
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Shandong, China, 250031
    • Shandong Provincial Third Hospital
  • Shanghai, China, 200032
    • Affiliated Zhongshan Hospital of Fudan University
  • Shanghai, China, 200081
    • The Third Affiliated Hospital of the Chinese PLA
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital
  • Weifang, China, 261000
    • Weifang People's Hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Zhengzhou, China, 450052
    • The First Affiliated Hospital of Zhengzhou University
• France
  • Besançon, France, 25030
    • Oncologie médicale Hopital Jean Minjoz
  • Brest, France, 29200
    • Institut de Cancerologie et d'Hematologie Hopital Morvan - CHRU de Brest
  • Marseille, France, 13385
    • Hopitaux de La Timone
  • Poitiers, France, 86000
    • Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie
  • Villejuif, France, 94805
    • Département De Médecine
• Italy
  • Candiolo, Italy, 10060
    • Fondazione del Piemonte per l'Oncologia (IRCCS)
  • Milan, Italy, 20089
    • Istituto Clinico Humanitas
  • Milan, Italy, 20133
    • Istituto Nazionale dei Tumori
  • Padua, Italy, 35128
    • Istituto Oncologico Veneto - I.R.C.C.S.
• South Korea
  • Jinju, South Korea, 52727
    • Gyeongsang National University Hospital
  • Pusan, South Korea, 49241
    • Pusan National University Hospital
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08916
    • Universitario Germans Trias i Pujol
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofía
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28041
    • Hospital Universitario Doce de Octubre
  • Sabadell, Spain, 08208
    • Corporacio Sanitaria Parc Tauli
  • Zaragoza, Spain, 50009
    • Hospital Miguel Servet
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals (Uclh)
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 95724
      • University of Arizona Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Florida
    • Orlando, Florida, United States, 32804
      • Advent Health Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center - Hospital
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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%.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZW25 (Zanidatamab) Monotherapy	Drug: ZW25 (Zanidatamab); Administered intravenously; Other Names: ZW25; JZP598; ZIIHERA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 45 months
DOR ≥ 16 Weeks by ICR	Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1	24 weeks, up to 45 months
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	Up to 45 months
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	Up to 45 months
ORR by Investigator Assessment	Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1	Up to 45 months
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	Up to 45 months
DOR ≥ 16 Weeks by Investigator Assessment	Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1	24 weeks, up to 45 months
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	Up to 45 months
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	Up to 45 months
Overall Survival	The time from the first dose of study treatment until the date of death from any cause	Up to 45 months
Incidence of Adverse Events (AEs)	Number of subjects who experienced AEs or serious adverse events	Up to 45 months
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	Up to 45 months
Maximum Serum Concentration of ZW25		Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose
Trough Concentration of ZW25	Minimum observed serum concentration (trough)	Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose
Incidence of Anti-drug Antibodies (ADAs)	Number of subjects who develop ADAs	Up to 45 months

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: BeiGene; Jazz Pharmaceuticals Ireland Limited; BeOne Medicines LTD
• Investigators: Study Director: Phillip Garfin, MD, PhD, Zymeworks Inc.; Study Director: Jiafang Ma, MD, BeiGene, Ltd.

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): July 11, 2024

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: HER2; Immunotherapy; Biliary Tract Cancer; Bispecific antibody; Biparatopic antibody; Intra-hepatic cholangiocarcinoma; Extra-hepatic cholangiocarcinoma; Gallbladder cancer; JZP598
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Gallbladder Diseases; Biliary Tract Neoplasms; Gallbladder Neoplasms; zanidatamab
• Other Study ID Numbers: ZWI-ZW25-203; 2020-000459-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No