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

Study Overview
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Brief Summary
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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.

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

Conditions
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Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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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: 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |