Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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The primary objective of this study is to determine the maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D), and safety and tolerability of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL by dose escalating lenalidomide

Official Title
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A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study of Bruton Tyrosine Kinase (BTK) Inhibitor, Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Conditions
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Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP). Relapsed or refractory disease, defined as either: 1) progression of disease after having achieved disease remission (complete response [CR] or partial response [PR]) , or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment regimen preceding entry to the study. Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT. Measurable disease as defined by at least 1 lymph node >1.5 cm in longest diameter, or at least 1 extra-nodal lesion >1.0 cm in longest diameter, and measurable in 2 perpendicular dimensions. Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody and an appropriate anthracycline-based combination therapy for at least 2 cycles, unless the patient is intolerant or had disease progression before Cycle 2.. Key Exclusion Criteria: Current or history of central nervous system (CNS) lymphoma. Histologically transformed lymphoma. History of allogeneic stem-cell transplantation. Prior exposure to a BTK inhibitor. Prior exposure to lenalidomide or thalidomide. 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 : Zanubrutinib + Lenalidomide<br>Zanubrutinib for up to 48 months Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months | Drug: Zanubrutinib<br>* 160 mg administered orally twice daily (BID)<br>* Other names: BGB-3111;Drug: Lenalidomide<br>* Administered as specified in the treatment arm<br>|
| Experimental: Part 2 : Zanubrutinib+Lenalidomide<br>Zanubrutinib for up to 48 months Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months | Drug: Zanubrutinib<br>* 160 mg administered orally twice daily (BID)<br>* Other names: BGB-3111;Drug: Lenalidomide<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants Experiencing Adverse Events (AEs) |  | Up to 48 months | 
| Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs) |  | Up to 48 months | 
| Part 2: Overall Response Rate (ORR) | The proportion of participants who achieve either a partial response (PR) or complete response (CR) | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Overall Response Rate (ORR) | The proportion of participants who achieve either a partial response (PR) or complete response (CR) | Up to 48 months | 
| Area Under the Curve from Zero to Last Measurable Concentration (AUC0-t) |  | Cycle 1 Day 1 (C1D1) and C1D21 up to 8 hours post-dose | 
| Maximum Concentration (Cmax) |  | C1D1 and C1D21 up to 8 hours post-dose | 
| Time to reach maximum plasma concentration (Tmax) |  | C1D1 and C1D21 up to 8 hours post-dose | 
| Apparent Clearance (CL/F) |  | C1D1 and C1D21 up to 8 hours post-dose | 
| Receptor Occupancy (Ro) |  | C1D1 and C1D21 up to 8 hours post-dose | 
| Complete Response Rate (CRR) |  | Up to 48 months | 
| Time to Response (TTR) |  | Up to 48 months | 
| Progression-Free Survival (PFS) |  | Up to 48 months | 
| Duration of Response (DOR) |  | Up to 48 months |