Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib

Study Overview
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Brief Summary
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Study consists of a single arm to explore the efficacy and safety of zanubrutinib in participants with CD79B mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

Official Title
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A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Bruton Tyrosine Kinase Inhibitor Zanubrutinib in Patients With CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Conditions
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Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed DLBCL based on the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissue. Positive CD79B mutation confirmed by the central laboratory. Previously received at least 1 line of adequate systemic anti-DLBCL therapy, defined as an anti-CD20 antibody-based chemoimmunotherapy for at least 2 consecutive cycles, unless participants had disease progression before Cycle 2 Relapsed or refractory (R/R) disease before study entry, defined as either Recurrent disease after having achieved disease remission (CR or partial response [PR]) at the completion of the latest treatment regimen. Stable disease or PD at the completion of the latest treatment regimen Ineligible for high dose therapy/stem cell transplantation, which is defined as meeting any of the following criteria: Significant organ dysfunction (eg, left ventricular ejection fraction < 50% by echocardiogram or multiple gated acquisition scan [MUGA], diffuse lung capacity for carbon monoxide < 60% predicted by pulmonary function test, creatinine clearance < 70 mL/min shown by nuclear medicine scan or 24-hour urine collection) or comorbidities precluding the use of high dose therapy/stem cell transplantation on the basis of unacceptable risk of treatment-related morbidity Failure to achieve CR or PR with salvage therapy. Failure to collect stem cells or unable to perform stem cell collection as assessed by the investigator. Exclusion Criteria: Participants who have NHL other than classical histology DLBCL (DLBCL, not otherwise specified), eg, participants with DLBCL transformed from indolent lymphomas, primary mediastinal (thymic) large B-cell lymphoma, primary cutaneous DLBCL, primary effusion lymphoma, and central nervous system (CNS) lymphoma. History of allogeneic stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor. Receipt of the following treatment at the time indicated before the first dose of study drug: Corticosteroid given with antineoplastic intent within 2 weeks, but a short course (≤ 7 days) of systemic corticosteroid treatment at doses ≤ 20 mg/day prednisone equivalent for control of lymphoma-related symptoms is allowed prior to enrollment provided that it is tapered off within 5 days after initiation of study treatment. Chemotherapy or radiotherapy within 2 weeks. Monoclonal antibody within 2 weeks. Investigational therapy within 2 weeks. Chinese patent medicine with antineoplastic intent within 2 weeks. History of other active malignancies within 2 years before study entry, with the exception of (1) adequately treated in-situ carcinoma of the cervix; (2) localized basal cell or squamous cell carcinoma of the skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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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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>administered orally | Drug: Zanubrutinib<br>* administered orally as capsules<br>* Other names: Brukinsa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Defined as the proportion of participants who achieved complete response (CR) or partial response (PR) by investigator assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL). | approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Defined as the proportion of participants who achieved complete response (CR) or partial response (PR) by Independent Review Committee assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL). | approximately 3.5 years | 
| Complete response rate (CRR) | Defined as the proportion of participants with a documented CR determined by the Independent Review Committee and by investigator assessment | approximately 3.5 years | 
| Duration of response (DOR) | DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death, whichever occurs first. Determined by the Independent Review Committee and by investigator assessment | approximately 3.5 years | 
| Progression-free survival (PFS) | PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first as determined by the Independent Review Committee and by investigator assessment | approximately 3.5 years | 
| Time to response (TTR) | TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better as determined by the Independent Review Committee and by investigator assessment | approximately 3.5 years | 
| Overall survival (OS) | OS defined as the time from start of treatment to the date of death due to any cause | approximately 3.5 years | 
| Number of participants with adverse events | Number of participants with adverse events and serious adverse events, including clinical laboratory measurements, physical examination, and vital signs | approximately 3.5 years |