A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers (HERIZON-BTC-01)
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|ClinicalTrials.gov Identifier: NCT04466891|
Recruitment Status : Active, not recruiting
First Posted : July 10, 2020
Last Update Posted : February 1, 2023
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|Condition or disease||Intervention/treatment||Phase|
|HER2-amplified Biliary Tract Cancers||Drug: ZW25 (Zanidatamab) Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay||Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||87 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||single-arm, open-label, multi-cohort, multicenter study|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers|
|Actual Study Start Date :||October 1, 2020|
|Actual Primary Completion Date :||October 10, 2022|
|Estimated Study Completion Date :||June 2024|
|Experimental: ZW25 (Zanidatamab) Monotherapy||
Drug: ZW25 (Zanidatamab)
Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
Subjects will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay
Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Subjects will be tested for HER2 protein-expression using the IHC-based companion diagnostic assay
- Confirmed objective response rate (ORR) by independent central review (ICR) [ Time Frame: Up to 2.5 years ]Number of subjects 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
- Duration of response (DOR) by ICR [ Time Frame: Up to 2.5 years ]The time from the first objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, clinical progression, or death from any cause
- DOR at ≥ 16 weeks by ICR [ Time Frame: 24 weeks to 2.5 years ]Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
- Disease control rate (DCR) by ICR [ Time Frame: Up to 2.5 years ]Number of subjects who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
- Progression-free survival (PFS) by ICR [ Time Frame: Up to 2.5 years ]The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause
- ORR by investigator assessment [ Time Frame: Up to 2.5 years ]Number of subjects who achieved a BOR of either CR or PR during treatment per RECIST 1.1
- DOR by investigator assessment [ Time Frame: Up to 2.5 years ]The time from the first objective response (CR or PR) to documented PD per RECIST 1.1, clinical progression, or death from any cause
- DOR at ≥ 16 weeks by investigator assessment [ Time Frame: 24 weeks to 2.5 years ]Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
- DCR by investigator assessment [ Time Frame: Up to 2.5 years ]Number of subjects who achieved a best response of CR, PR, or SD during treatment per RECIST 1.1
- PFS by investigator assessment [ Time Frame: Up to 2.5 years ]The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause
- Overall survival [ Time Frame: Up to 2.5 years ]The time from the first dose of study treatment until the date of death from any cause
- Incidence of adverse events (AEs) [ Time Frame: Up to 2.5 years ]Number of subjects who experienced AEs or serious adverse events
- Incidence of laboratory abnormalities [ Time Frame: Up to 2.5 years ]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
- Maximum serum concentration of ZW25 [ Time Frame: Up to 2.5 years ]
- Trough concentration of ZW25 [ Time Frame: Up to 2.5 years ]Minimum observed serum concentration (trough)
- Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2.5 years ]Number of subjects who develop ADAs
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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%.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04466891
|Study Director:||Phillip Garfin, MD, PhD||Zymeworks Inc.|
|Study Director:||Jiafang Ma, MD||BeiGene, Ltd.|
|Responsible Party:||Zymeworks Inc.|
|Other Study ID Numbers:||
2020-000459-11 ( EudraCT Number )
|First Posted:||July 10, 2020 Key Record Dates|
|Last Update Posted:||February 1, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||Yes|
|Device Product Not Approved or Cleared by U.S. FDA:||Yes|
Biliary Tract Cancer
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases