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Trial record 1 of 1 for:    ZWI-ZW25-203
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A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

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ClinicalTrials.gov Identifier: NCT04466891
Recruitment Status : Recruiting
First Posted : July 10, 2020
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
BeiGene, Ltd.
Information provided by (Responsible Party):
Zymeworks Inc.

Tracking Information
First Submitted Date  ICMJE July 6, 2020
First Posted Date  ICMJE July 10, 2020
Last Update Posted Date May 11, 2021
Actual Study Start Date  ICMJE October 1, 2020
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2020)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers
Official Title  ICMJE A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
single-arm, open-label, multi-cohort, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-amplified Biliary Tract Cancers
Intervention  ICMJE
  • Drug: ZW25 (Zanidatamab)
    Administered intravenously
  • 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
Study Arms  ICMJE Experimental: ZW25 (Zanidatamab) Monotherapy
Interventions:
  • Drug: ZW25 (Zanidatamab)
  • Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
  • Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 regimen of systemic therapy for advanced disease, including 1 gemcitabine-containing regimen, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who have received prior adjuvant or neoadjuvant treatment, if progression has occurred < 6 months from completion of the adjuvant or neoadjuvant therapy, this regimen will be considered as 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, biloma or abscess. Any complications should be resolved within 2 weeks prior to the first dose of ZW25.
  • Prior or concurrent invasive 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com
Listed Location Countries  ICMJE Canada,   Chile,   China,   France,   Italy,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04466891
Other Study ID Numbers  ICMJE ZWI-ZW25-203
2020-000459-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zymeworks Inc.
Study Sponsor  ICMJE Zymeworks Inc.
Collaborators  ICMJE BeiGene, Ltd.
Investigators  ICMJE
Study Director: Neil Josephson, MD Zymeworks Inc.
PRS Account Zymeworks Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP