Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies

Study Overview
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Brief Summary
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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.

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

Conditions
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Mature B-cell Malignancies

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zanubrutinib<br> | Drug: Zanubrutinib<br>* Zanubrutinib at 160 mg orally twice daily<br>* Other names: BGB-3111;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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