Observational Study Evaluating the Efficacy and Safety of Zanubrutinib in Participants With Waldenström Macroglobulinemia

A Phase 4, Observational Study Evaluating the Efficacy and Safety of the Bruton Tyrosine Kinase (BTK) Inhibitor Zanubrutinib in Patients With Waldenström Macroglobulinemia

This is a hybrid (retrospective and prospective) non-interventional registry study to further describe the clinical profile of zanubrutinib in Waldenström macroglobulinemia (WM) participants with and without specific mutations and from racial and ethnic minority groups. Data collected from this registry study will be used to better understand the clinical benefit and safety of zanubrutinib for the treatment of participants in these populations.

Study Overview

• Status: Recruiting
• Conditions: Waldenstrom Macroglobulinemia
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Observational
• Enrollment (Estimated): 111

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1-877-828-5568; Email: clinicaltrials@beigene.com

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Pan American Oncology Trials, LLC
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805-2606
      • Recruiting
      • Clearview Cancer Institute
    • Mobile, Alabama, United States, 36604-1405
      • Recruiting
      • South Alabama Medical Science Foundation Mitchell Cancer Institute
  • California
    • Duarte, California, United States, 91010-3012
      • Recruiting
      • City of Hope National Medical Center
    • Glendale, California, United States, 91204-3640
      • Recruiting
      • Los Angeles Cancer Network (LACN)
    • Rancho Mirage, California, United States, 92270-3221
      • Recruiting
      • Eisenhower Medical Center, Lucy Curci Cancer Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401-7233
      • Recruiting
      • Hattiesburg Hematology and Oncology Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89169-3321
      • Recruiting
      • Comprehensive Cancer Centers of Nevada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult participants with WM who are either already receiving or are planned to start treatment with zanubrutinib

Description

Inclusion Criteria:

• Clinical and definitive histologic diagnosis of WM
• Measurable disease, as defined by a serum immunoglobulin M (IgM) level > 0.5 g/dL at the time of zanubrutinib initiation
• Started treatment with zanubrutinib, has been treated with zanubrutinib, or is planned to be prescribed zanubrutinib for the treatment of WM

• Bone marrow specimens with central MYD88 test results of:

  1. Cohort 1: MYD88 L265P mutation; enrollment of TN participants will be stopped in each racial and ethnic participant group when the required numbers of participants in the group are met
  2. Cohort 2: non-L265P MYD88 mutation(s) and MYD88WT

Exclusion Criteria:

• Evidence of disease transformation before the first dose of zanubrutinib
• Evidence of other non-Hodgkin Lymphoma (NHL) subtypes
• Prior or concurrent active malignancy ≤ 2 years before the first dose of zanubrutinib, except for malignancies that, in the investigator's opinion, will not obscure the interpretation of safety or efficacy results
• Concurrent participation in another therapeutic clinical study while receiving zanubrutinib, although the participant may be eligible depending on the status of the interventional study after discussion with the Medical Monitor or designee on an individual basis

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: MYD88 L265P mutation; Arm A: Treatment-naïve (TN); Arm B: Relapsed/refractory (R/R)	Drug: Zanubrutinib; Dosing and treatment duration are at the discretion of the prescribing physician and in accordance with local labeling; Other Names: Brukinsa; BGB-3111
Cohort 2: Non-L265P MYD88 mutation(s) and MYD88 wildtype; Arm C: TN and R/R	Drug: Zanubrutinib; Dosing and treatment duration are at the discretion of the prescribing physician and in accordance with local labeling; Other Names: Brukinsa; BGB-3111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Response Rate (MRR)	MRR is defined as the proportion of participants achieving either complete response (CR), very good partial response (VGPR), or partial response (PR) as determined by the investigator using an adaptation of the response criteria updated at the Sixth International Workshop on WM (IWWM)	Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VGPR+ Rate	VGPR+ rate is defined as the proportion of participants achieving either CR or VGPR	Up to approximately 5 years
Overall Response Rate (ORR)	ORR is defined as the proportion of participants achieving either CR, VGPR, PR, or minor response (MR)	Up to approximately 5 years
Duration of Response (DOR)	DOR is defined as the time from the first determination of response (CR, VGPR, or PR) until first documentation of or death, whichever comes first	Up to approximately 5 years
Number of Participants with Treatment-emergent Adverse Events		Up to approximately 5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Waldenstrom Macroglobulinemia; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-3111-402

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No