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

NCT ID: NCT04466891

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2024-07-11

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).

Conditions

HER2-amplified Biliary Tract Cancers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ZW25 (Zanidatamab) Monotherapy

Group Type: EXPERIMENTAL

ZW25 (Zanidatamab)

Intervention Type: DRUG

Administered intravenously

Interventions

ZW25 (Zanidatamab)

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

JZP598; ZW25; ZIIHERA®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: collaborator

Jazz Pharmaceuticals Ireland Limited

INDUSTRY

Sponsor Role: collaborator

BeOne Medicines LTD

UNKNOWN

Sponsor Role: collaborator

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

University of Arizona Cancer Center

Tucson, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

University of California Los Angeles

Santa Monica, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Advent Health Cancer Institute

Orlando, Florida, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Texas Southwestern Medical Center - Hospital

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Centro de Cáncer Nuestra Señora de la Esperanza

Santiago, , Chile

Radiomed (Clinica Alemana de Temuco)

Temuco, , Chile

Beijing Cancer Hospital

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

Jilin Cancer Hospital

Changchun, , China

Hunan Cancer Hospital

Changsha, , China

West China Hospital

Chengdu, , China

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, , China

The First Affiliated Hospital of Zhejiang University

Hangzhou, , China

Zhejiang Provincial People's Hospital

Hangzhou, , China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Affiliated Tumor Hospital of Harbin Medical University

Harbin, , China

Anhui Provincial Hospital

Hefei, , China

Huzhou Central Hospital

Huzhou, , China

Jinhua Central Hospital

Jinhua, , China

The First Hospital Of Lanzhou University

Lanzhou, , China

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

Nanjing, , China

Shandong Provincial Third Hospital

Shandong, , China

Affiliated Zhongshan Hospital of Fudan University

Shanghai, , China

The Third Affiliated Hospital of the Chinese PLA

Shanghai, , China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, , China

Weifang People's Hospital

Weifang, , China

Hubei Cancer Hospital

Wuhan, , China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Oncologie médicale Hopital Jean Minjoz

Besançon, , France

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

Brest, , France

Hopitaux de La Timone

Marseille, , France

Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie

Poitiers, , France

Département De Médecine

Villejuif, , France

Fondazione del Piemonte per l'Oncologia (IRCCS)

Candiolo, , Italy

Istituto Clinico Humanitas

Milan, , Italy

Istituto Nazionale Dei Tumori

Milan, , Italy

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

Padua, , Italy

Gyeongsang National University Hospital

Jinju, , South Korea

Pusan National University Hospital

Pusan, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

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

Seoul, , South Korea

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Universitario Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Doce de Octubre

Madrid, , Spain

Corporacio Sanitaria Parc Tauli

Sabadell, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

University College London Hospitals (UCLH)

London, , United Kingdom

Royal Free London NHS Foundation Trust

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United States; Canada; Chile; China; France; Italy; South Korea; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39114870 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37276871 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000459-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ZWI-ZW25-203

Identifier Type: -

Identifier Source: org_study_id