TriangleNCT04466891 · CITED IN SOURCE DOCUMENTS
A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2025-09-15
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)
Duration of Response (DOR) by ICR
DOR ≥ 16 Weeks by ICR
Disease Control Rate (DCR) by ICR
Progression-free Survival (PFS) by ICR
ORR by Investigator Assessment
DOR by Investigator Assessment
DOR ≥ 16 Weeks by Investigator Assessment
DCR by Investigator Assessment
PFS by Investigator Assessment
Overall Survival
Incidence of Adverse Events (AEs)
Incidence of Laboratory Abnormalities
Maximum Serum Concentration of ZW25
Trough Concentration of ZW25
Incidence of Anti-drug Antibodies (ADAs)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: ZW25 (Zanidatamab)
- label
- ZW25 (Zanidatamab) Monotherapy
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- ZW25 (Zanidatamab) Monotherapy
- description
- Administered intravenously
- name
- ZW25 (Zanidatamab)
- other Names
- JZP598
- ZW25
- ZIIHERA®
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- intervention Model Description
- single-arm, open-label, multi-cohort, multicenter study
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 87
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)
- time Frame
- Up to 34 months
- secondary Outcomes
- description
- 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
- measure
- Duration of Response (DOR) by ICR
- time Frame
- Up to 45 months
- description
- Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
- measure
- DOR ≥ 16 Weeks by ICR
- time Frame
- 24 weeks, up to 45 months
- description
- 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
- measure
- Disease Control Rate (DCR) by ICR
- time Frame
- Up to 45 months
- description
- 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
- measure
- Progression-free Survival (PFS) by ICR
- time Frame
- Up to 45 months
- description
- Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1
- measure
- ORR by Investigator Assessment
- time Frame
- Up to 45 months
- description
- 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
- measure
- DOR by Investigator Assessment
- time Frame
- Up to 45 months
- description
- Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
- measure
- DOR ≥ 16 Weeks by Investigator Assessment
- time Frame
- 24 weeks, up to 45 months
- description
- 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
- measure
- DCR by Investigator Assessment
- time Frame
- Up to 45 months
- description
- 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
- measure
- PFS by Investigator Assessment
- time Frame
- Up to 45 months
- description
- The time from the first dose of study treatment until the date of death from any cause
- measure
- Overall Survival
- time Frame
- Up to 45 months
- description
- Number of subjects who experienced AEs or serious adverse events
- measure
- Incidence of Adverse Events (AEs)
- time Frame
- Up to 45 months
- description
- 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
- measure
- Incidence of Laboratory Abnormalities
- time Frame
- Up to 45 months
Full study description
- 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).
Source references
- references
- citation
- 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
- 39114870
- type
- DERIVED
- citation
- 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.
- pmid
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- type
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Source notices and limitations
Discovery and provenance
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- targeted therapy</h5> <div class="pdq-content-list"><ol id="_609"><li> The international, multicenter, single-arm, phase IIb <a href="/clinicaltrials/NCT04466891">HERIZON-BTC-01</a> trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence <em>in situ</em> hybridization), unresectable, locally advanc
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- ry Tract Cancer (BTC) The efficacy of ZIIHERA was evaluated in 62 patients with HER2-positive (IHC 3+ by central assessment) BTC in Cohort 1 of HERIZON‑BTC‑01 (NCT04466891), an open-label, multicenter, single arm trial in patients with unresectable or metastatic disease. Patients were required to have received at least one prior
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Preserved source evidence · Not medical advice