Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies

A Phase 1/2 Study of Zanubrutinib in Japanese Patients With Mature B-Cell Malignancies

This is a Phase 1/2 study of zanubrutinib in Japanese participants with mature B-cell malignancies.

This study intends to assess the use of zanubrutinib as an investigational agent to develop new treatment options for Japanese participants with B-cell malignancies. No formal hypothesis testing will be performed given the small sample size.

Study Overview

• Status: Completed
• Conditions: Mature B-cell Malignancies
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Gifu, Japan, 500-8513
    • Gifu Municipal Hospital
  • Nagasaki, Japan, 852-8511
    • The Japanese Red Cross Nagasaki Genbaku Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Yokohama, Japan, 221-0855
    • Yokohama Municipal Citizens Hospital
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital
    • Toyohashishi, Aichi-ken, Japan, 441-8570
      • Toyohashi Municipal Hospital
  • Chiba
    • Chiba, Chiba, Japan, 260-8717
      • Chiba cancer center
  • Ehime
    • Matsuyama, Ehime, Japan, 790 8524
      • Matsuyama Red Cross Hospital
  • Fukuoka
    • KurumeShi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
    • Sapporo, Hokkaido, Japan, 064-0804
      • Aiiku Hospital
  • Hyōgo
    • KobeShi, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa cancer center
  • Tokyo
    • ChuoKu, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants with Confirmed diagnosis of mature B-cell neoplasms including chronic lymphocytic leukemia/ small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma and Waldenström's macroglobulinemia
• Relapsed/refractory disease defined as disease that relapsed after, or been refractory to, at least 1 prior therapy
• Meeting at least one of criteria for requiring treatment
• Measurable disease by computed tomography (CT)/ magnetic resonance imaging (MRI) for mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) participants and by serum immunoglobulin (Ig) M level > 0.5 g/dL for WM participants
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2
• Life expectancy of > 4 months

Key Exclusion Criteria:

• Known central nervous system involvement by lymphoma/leukemia
• Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
• Prior allogeneic stem cell transplant
• Systemic chemotherapy or radiation therapy within 2 weeks prior to first dose of zanubrutinib
• Active fungal, bacterial, and/or viral infection requiring systemic therapy
• Prior therapy with B-cell receptor inhibitor (eg, Bruton tyrosine kinase, phosphoinositide 3 kinase delta, and/or spleen tyrosine kinase inhibitor) or B-cell lymphoma 2 inhibitor (eg, venetoclax/ABT-199)
• Pregnant, lactating, or nursing women
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib	Drug: Zanubrutinib; Zanubrutinib at 160 mg orally twice daily; Other Names: BGB-3111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation of Treatment	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Maximum Plasma Concentration (Cmax) of zanubrutinib	Up to 29 days
Part 1: Area under plasma concentration-time curve Concentration (AUC) of zanubrutinib	Up to 29 days
Part 2: Overall response rate as assessed by Independent Review Committee (IRC)	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1: Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells	Predose up to 24 hours postdose
Part 1: Overall response rate (ORR) as assessed by the investigator	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Progression-free survival (PFS) as assessed by the investigator	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Duration of response as assessed by the investigator	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 1: Time to response as assessed by the investigator	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Maximum Plasma Concentration (Cmax) of zanubrutinib	Predose up to 24 hours postdose Cycle 1 day 1 (C1D1) and Cycle 2 day 1 (C2D1)
Part 2: Number of Participants Experiencing AEs Leading to Discontinuation of Treatment	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Rate of complete response for chronic lymphocytic leukemia (CLL) as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Rate of complete response with incomplete marrow for CLL as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Rate of complete response for small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Rate of very good partial response (VGPR) or better for WM as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Major response rate (partial response or better) for WM as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Rate of partial response or better for CLL as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Overall response rate (ORR) by disease type as assessed by the investigator	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Progression-free survival (PFS) as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Duration of response as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
Part 2: Time to response as assessed by IRC	Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier
To assess the efficacy of zanubrutinib as measured by overall survival	Overall survival defined as time from start of study treatment to death due to any cause

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): May 10, 2023
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: relapsed/refractory chronic lymphocytic leukemia; relapsed/refractory small lymphocytic lymphoma; treatment-naïve chronic lymphocytic leukemia; treatment-naïve /small lymphocytic lymphoma; relapsed/refractory mantle cell lymphoma; relapsed/refractory marginal zone lymphoma; relapsed/refractory follicular lymphoma; relapsed/refractory Waldenström macroglobulinemia; treatment-naïve Waldenström macroglobulinemia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-3111-111; JapicCTI-195047 (Registry Identifier: Jape)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No