Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-000459-11
    Sponsor's Protocol Code Number:ZWI-ZW25-203
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-06-12
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2020-000459-11
    A.3Full title of the trial
    A Phase 2b, open-label, single-arm study of ZW25 monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    ZW25 in Subjects with Advanced or Metastatic HER2-Amplified Biliary Tract Cancer
    A.4.1Sponsor's protocol code numberZWI-ZW25-203
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorZymeworks Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportZymeworks Inc
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD
    B.5.2Functional name of contact pointDenis Ushakov
    B.5.3 Address:
    B.5.3.1Street Address3900 PPD Paramount Parkway
    B.5.3.2Town/ cityMorrisville
    B.5.3.3Post code27560
    B.5.3.4CountryUnited States
    B.5.4Telephone number19194759815
    B.5.6E-maildenis.ushakov@ppdi.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameZanidatamab
    D.3.2Product code ZW25
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZanidatamab
    D.3.9.1CAS number 2169946-15-8
    D.3.9.2Current sponsor codeZW25
    D.3.9.3Other descriptive nameA bispecific antibody recognizing two non-overlapping epitopes of the extracellular domain of the human HER2 antigen
    D.3.9.4EV Substance CodeSUB203836
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects with HER2-amplified, inoperable and advanced or metastatic Biliary Tract Cancer (BTC), ZW25 in Subjects with Advanced or Metastatic HER2-Amplified Biliary Tract Cancer
    E.1.1.1Medical condition in easily understood language
    Inoperable and advanced or metastatic Biliary Tract Cancer patients that overexpress the HER2 protein including intra-hepatic cholangiocarcinoma, extra heaptic cholangiocarcinoma and gallbladder.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the anti-tumor activity of ZW25 monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers (BTC)
    E.2.2Secondary objectives of the trial
    To further evaluate the anti-tumor activity of ZW25 monotherapy in subjects with advanced or metastatic HER2-amplified BTC
    To evaluate the safety and tolerability of ZW25 monotherapy in subjects with advanced or metastatic HER2-amplified BTC
    To evaluate the pharmacokinetics (PK) of ZW25
    To evaluate the immunogenicity of ZW25
    Exploratory:
    To evaluate the anti-tumor activity of ZW25 monotherapy by BTC anatomical subtype
    To evaluate the utility of potential serum and tumor biomarkers
    To evaluate the effect of ZW25 treatment on quality of life (QOL)
    To evaluate the effect of ZW25 treatment on disease-related pain and opioid use for pain control
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC.
    2.Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
    3.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.
    4.Subjects must have at least 1 measurable target lesion by RECIST 1.1. Subjects who have received prior local therapy (embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or is within the treatment field and has shown ≥20% growth in size since post-treatment assessments.
    5.Subjects must test positive for HER2 amplification by in situ hybridization (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.
    6.Male or female, ≥18 years of age (or the legal age of adulthood per country-specific regulations).
    7.Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
    8.Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥1.5 x 109/L, platelet count ≥75 x 109/L (not requiring transfusion support), and hemoglobin (Hgb) ≥9 g/dL (subjects with chronic anemia that is supported by intermittent red blood cell [RBC] transfusions are eligible).
    9.Liver function: serum bilirubin ≤1.5 x the upper limit of normal (ULN) or ≤3 x ULN for subjects with Gilbert’s disease, aspartate aminotransferase (AST) ≤3 x ULN, and alanine aminotransferase (ALT) ≤3 x ULN. For subjects with liver involvement, AST and ALT ≤5.0 x ULN is acceptable.
    10.Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥50%.
    11.Kidney function: glomerular filtration rate (GFR) ≥30 mL/min as estimated by the Modification of Diet in Renal Disease (MDRD) equation .
    12.Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β hCG) pregnancy test result within 3 days prior to the first dose of ZW25. Females with false positive urine test results can be enrolled if subsequent serum testing is negative .
    13.For female subjects who are not surgically sterile or post-menopausal and for male subjects with a partner of child-bearing potential, willingness for the couple to use 2 methods of birth control with a failure rate of less than 1% per year during the study and for 12 months after the last dose of ZW25. These include, but are not limited to, established use of oral, implanted, or injected hormonal contraceptives or placement of intra-uterine device or intra-uterine system
    14.Male subjects must agree to not donate sperm and female subjects must agree to not donate oocytes starting at screening and throughout the study period, and for at least 12 months after the last dose of ZW25
    15.The subject or subject’s legally acceptable representative must provide written informed consent. Subjects who elect to be pre-screened for HER2 status must provide a separate written informed consent for collection, storage, and analysis of the tumor tissue.
    E.4Principal exclusion criteria
    1.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.
    2.Had major surgery within 4 weeks of the first dose of ZW25.
    3.Prior treatment with HER2-targeted agents.
    4.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).
    5.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.
    6.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.
    7.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.
    8.Significant acute infection or chronic infections that have not stabilized with treatment.
    9.Active hepatitis, including the following:
    a.Acute or chronic hepatitis B (Exception: subjects who are hepatitis B surface antigen positive are eligible if they have HBV DNA less than 500 IU/mL)
    b.Infection with hepatitis C (Exception [i] subjects who have no history of curative viral treatment and are documented to be viral load negative are eligible; [ii] subjects who have completed curative viral therapy ≥12 weeks prior to enrollment, and viral load is negative are eligible)
    10.Infection with human immunodeficiency virus (HIV)-1 or HIV-2 (Exception: subjects with well-controlled HIV [e.g., CD4 >350/mm3 and undetectable viral load] are eligible).
    11.Females who are breastfeeding or pregnant, and females and males planning a pregnancy.
    12.History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of ZW25.
    13.Treatment with anthracyclines within 90 days before first dose of ZW25 and/or total lifetime load exceeding 360 mg/m2 Adriamycin® or equivalent.
    14.Use of corticosteroids administered at doses equivalent to >15 mg per day of prednisone within 2 weeks of first ZW25 dosing unless otherwise approved by the medical monitor. Topical, ocular, intra-articular, intranasal, and/or inhalational corticosteroids are permitted.
    15.Ongoing, clinically significant toxicity (Grade 2 or higher) associated with prior cancer therapies, with the following exceptions:
    a.Alopecia
    b.Congestive heart failure (CHF), which must have been ≤ Grade 1 at the time of occurrence and which must have completely resolved
    16.QTc Fridericia (QTcF) >470 ms.
    17.History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic CHF.
    18.Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.
    19.Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
    E.5 End points
    E.5.1Primary end point(s)
    Confirmed objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by independent central review (ICR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Disease response will be assessed according to RECIST 1.1 by ICR; responses are to be confirmed 4 weeks following initial documentation of objective response by the investigator.
    E.5.2Secondary end point(s)
    Duration of response (DOR) by RECIST 1.1 assessed by ICR
    Proportion of subjects with a DOR ≥16 weeks by RECIST 1.1 assessed by ICR
    Disease control rate (DCR) by RECIST 1.1 assessed by ICR
    Progression-free survival (PFS) by RECIST 1.1 assessed by ICR
    ORR by RECIST 1.1 assessed by investigator
    DOR by RECIST 1.1 assessed by investigator
    Proportion of subjects with a DOR ≥16 weeks by RECIST 1.1 assessed by investigator
    DCR by RECIST 1.1 assessed by investigator
    PFS by RECIST 1.1 assessed by investigator
    Overall survival (OS)
    Frequency and severity of adverse events (AEs)
    Frequency of serious adverse events (SAEs) and deaths
    Frequency and severity of clinical laboratory abnormalities
    Frequency of dose modifications of ZW25
    Serum concentrations of ZW25 as a function of time post-dosing
    PK parameters for single (first) dose and multiple doses
    Frequency, duration, and time of onset of anti-drug antibodies (ADA) and neutralizing antibodies, if applicable

    Exploratory
    Confirmed ORR and DOR by RECIST 1.1 and BTC anatomical subtype, as assessed by ICR
    Potential biomarkers predictive of response
    Patient-reported outcomes (PRO) per the European Quality of Life 5-Dimensions 5-level questionnaire (EQ-5D-5L)
    Change from baseline in opioid use
    Change from baseline in Brief Pain Inventory (BPI) domain scores

    E.5.2.1Timepoint(s) of evaluation of this end point
    Disease response (DOR,DCR,ORR, PFS) assessed according to RECIST 1.1 by PI. Responses 4 weeks following initial documentation of objective response by PI.
    Safety will be monitored by recording the type, frequency, and severity of AEs as well as SAEs and deaths.
    ZW25 Serum concentrations as a function of time post-dosing
    ADA on day 1 & 15 Cycle 1 & 2, and day 1 Cycle 4 and every even cycle thereafter
    Extensive PK day 1, 2, 5 & 15 Cycle 1, days 1 & 15 Cycle 2, day 1 of every even cycle thereafter, and EoT with less than 6 treatment months
    Sparse PK day 1 an&d 15 Cycle 1, and day 1 Cycle 4 and every even cycle thereafter, and EoT with less than 6 treatment months
    EQ-5D-5L and BPI Every 8 Weeks Timed from Cycle 1 Day 1
    Assessment of exploratory biomarkers at selected timepoints
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Chile
    China
    France
    Italy
    Korea, Republic of
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Subjects may continue on treatment with ZW25 until investigator-determined radiographic disease progression per RECIST 1.1, unequivocal clinical progression, unacceptable toxicity, consent withdrawal, physician decision, pregnancy, start of a subsequent anticancer therapy, or study termination by the sponsor.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Not different from normal treatment on this condition. Standard of care considered by the Investigator.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-10-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-08-24
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 11 06:27:56 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA