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    Summary
    EudraCT Number:2018-001284-24
    Sponsor's Protocol Code Number:BGB-3111-214
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-11-29
    Trial results View 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 number2018-001284-24
    A.3Full title of the trial
    A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients with Relapsed or Refractory Marginal Zone Lymphoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 Study in Patients with Relapsed or Refractory Marginal Zone Lymphoma
    A.4.1Sponsor's protocol code numberBGB-3111-214
    A.5.4Other Identifiers
    Name:USAN; Number:zanubrutinib
    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 SponsorBeiGene, Ltd.
    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 supportBeiGene, Ltd.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBeiGene, Ltd.
    B.5.2Functional name of contact pointBeiGene Clinical Support
    B.5.3 Address:
    B.5.3.1Street AddressUSA
    B.5.3.2Town/ cityUSA
    B.5.3.3Post codeUSA
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@beigene.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 nameZanubrutinib
    D.3.2Product code BGB-3111
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZanubrutinib
    D.3.9.1CAS number 1691249-45-2
    D.3.9.2Current sponsor codeBGB-3111
    D.3.9.4EV Substance CodeSUB184615
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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
    Relapsed or Refractory Marginal Zone Lymphoma
    E.1.1.1Medical condition in easily understood language
    Marginal zone lymphoma (MZL).
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10076596
    E.1.2Term Marginal zone lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of zanubrutinib in relapsed or refractory
    marginal zone lymphoma as measured by overall response rate in accordance with the Lugano
    Classification determined by independent central review
    E.2.2Secondary objectives of the trial
    - To evaluate the efficacy of zanubrutinib in relapsed or refractory marginal zone lymphoma in
    accordance with the Lugano Classification as measured by the following:
    - Overall response rate determined by investigator assessment
    - Progression-free survival
    - Overall survival
    - Duration of response
    - Time to response
    - Time to treatment failure
    - Time to next line of therapy for marginal zone lymphoma
    - To evaluate patient-reported outcomes
    - To determine the safety of zanubrutinib
    - To determine pharmacokinetics parameters of zanubrutinib
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each patient eligible to participate in this study must meet all the following criteria:
    1. Age 18 years or older
    2. Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes (nodal MZL enrollment is capped at 30 patients). Gastric MZL must be H. pylori-negative disease or H. pylori-positive disease that has remained stable, progressed, or relapsed following antibiotic therapy. Patients with a screening serum immunoelectrophoresis result indicating a monoclonal spike must have a possible diagnosis of Waldenström's macroglobulinemia ruled out.
    3. Previously received one or more lines of therapy including at least one CD20-directed regimen
    (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at
    least PR or documented PD after, the most recent systemic treatment
    4. Current need for systemic therapy for MZL in the opinion of the investigator
    5. Availability of archival tissue or consent to obtain fresh tumor tissue sample from an evaluable core or excisional biopsy (approximately 10 to 15 unstained formalin fixed paraffin embedded slides or tissue box).
    6. Measurable disease by CT or MRI. Measurable disease is defined as ≥ 1 nodal lesion > 1.5 cm in longest diameter and/or ≥ 1 extranodal lesion > 1.0 cm in longest diameter, and lesion(s) measurable in 2 perpendicular diameters. Patients with spleen-only disease are not considered to have measurable disease
    7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
    8. Life expectancy ≥ 6 months
    9. Adequate bone marrow function
    a. Absolute neutrophil count (ANC) ≥ 1,000/mm3 (growth factor use is allowed), except for patients with bone marrow involvement by MZL in which case ANC must be ≥ 750/mm3
    b. Platelet ≥ 75,000/mm3 (may not be post-transfusion), except for patients with bone marrow involvement by MZL in which case the platelet count must be ≥ 50,000/mm3
    10. Adequate organ function
    a. Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection)
    b. Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal (ULN) unless due to MZL
    c. Serum total bilirubin < 2.0 × ULN (unless documented Gilbert’s syndrome)
    11. Female patients of childbearing potential must have a negative pregnancy test at screening and must practice highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib. These
    methods are described in Section 4.1
    12. Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for ≥ 90 days after the last dose of zanubrutinib
    13. Ability to provide written informed consent and can understand and comply with the requirements of the study
    E.4Principal exclusion criteria
    Each patient eligible to participate in this study must not meet any of the following exclusion criteria:
    1. Known transformation to aggressive lymphoma, eg, large cell lymphoma. Clinically suspected transformation will require a biopsy of the suspected area prior to enrollment to confirm absence of transformation
    2. Clinically significant cardiovascular disease (as defined in Section 4.2)
    3. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer
    4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
    5. History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
    6. Severe or debilitating pulmonary disease
    7. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
    8. Active fungal, bacterial and/or viral infection requiring systemic therapy
    9. Known central nervous system involvement by lymphoma
    10. Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs
    11. Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection (as defined in Section 4.2)
    12. Major surgery within 4 weeks of the first dose of study drug
    13. Prior treatment with a Bruton tyrosine kinase (BTK) inhibitor
    14. Last dose of prior therapy for MZL ≤ 21 days prior to first dose of study drug, with the following additional exclusion requirements:
    a. Treatment with monoclonal antibody-based therapy within 28 days of first dose of study drug
    b. Treatment with chimeric antigen receptor T-cell therapy within 180 days of first dose of study drug
    c. Treatment with any herbal medicine with anti-neoplastic intent within 28 days of first dose of study drug
    d. Allogeneic hematopoietic stem cell transplantation within 12 months of first dose of study drug
    15. Any chemotherapy or radiation treatment for non-MZL indications within 21 days of first dose of study drug
    16. Toxicity from prior anti-cancer therapy that has not recovered to ≤ Grade 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count, see Inclusion criterion 9)
    17. Pregnant or lactating women
    18. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
    19. Ongoing alcohol or drug addiction
    20. Hypersensitivity to zanubrutinib or any of the other ingredients in zanubrutinib
    21. Requires ongoing treatment with a strong CYP3A inhibitor or inducer
    22. Received investigational drug within 30 days prior to first dose of zanubrutinib on this study or plans to receive another investigational drug during this study
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is ORR in accordance with the Lugano Classification and determined by independent central review.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Per protocol
    E.5.2Secondary end point(s)
    The secondary endpoints are:
    - ORR in accordance with the Lugano Classification determined by investigator assessment.
    - ORR accordance with the Lugano Classification using PET
    assessment data for patients with FDG–avid disease -avid disease determined by
    independent central review.
    - PFS in accordance with the Lugano Classification determined by independent central review and by investigator assessment
    - OS
    - DOR in accordance with the Lugano Classification determined by independent central review and by investigator assessment
    - TTR in accordance with the Lugano Classification determined by independent central review and by investigator assessment
    - Time to treatment failure
    - Time to next line of therapy for MZL
    - PROs measured by the EQ-5D-5L and EORTC QLQ-C30 questionnaire
    - Safety parameters including AEs, SAEs, laboratory tests, physical exams, and vital signs
    - PK parameters such as apparent clearance of the drug from plasma (CL/F) and AUC0-12
    Exploratory Endpoints:
    - ORR (CR + CRu +PR) in accordance determined by independent central review
    E.5.2.1Timepoint(s) of evaluation of this end point
    Per protocol
    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 No
    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 No
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Australia
    China
    France
    Italy
    New Zealand
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    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 months11
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    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: 28
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 37
    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 No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 65
    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)
    All patients will receive zanubrutinib at 160 mg orally twice daily (two 80-mg capsules orally twice daily), to be continued until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination. Each cycle consists of 28 days.
    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 Decision2019-01-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-22
    P. End of Trial
    P.End of Trial StatusOngoing
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