Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma

Study Overview
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Brief Summary
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This is a single arm study to evaluate the efficacy, safety and tolerability of zanubrutinib (BGB-3111) in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).

Official Title
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A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma

Conditions
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MZL, Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 18 years or older Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least partial response or documented progressive disease (PD) after, the most recent systemic treatment Current need for systemic therapy for MZL Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) Eastern Cooperative Oncology Group (ECOG) of 0-2 Life expectancy ≥ 6 months Adequate bone marrow function Adequate organ function Male and female participants must use highly effective methods of contraception Key Exclusion Criteria: Known transformation to aggressive lymphoma, eg, large cell lymphoma Clinically significant cardiovascular disease Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention History of stroke or intracranial hemorrhage Severe or debilitating pulmonary disease Active fungal, bacterial and/or viral infection requiring systemic therapy Known central nervous system involvement by lymphoma Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection Major surgery within 4 weeks of the first dose of study drug Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor Pregnant or lactating women Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer Concurrent participation in another therapeutic clinical trial 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>Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent | Drug: Zanubrutinib<br>* Zanubrutinib at a dose of 160 mg orally twice a day (BID)<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) by Independent Review Committee (IRC) Assessment | ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by an IRC using the Lugano Classification | Up to approximately 3 years and 2.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by Investigator Assessment | ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by the investigator using the Lugano Classification. | Up to approximately 3 years and 2.5 months | 
| ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT) | ORR is defined as the percentage of participants with complete and partial response as the best overall response, as determined by an IRC using PET-CT assessment data for participants with fluorodeoxyglucose (FDG)-avid disease | Up to approximately 3 years and 2.5 months | 
| Progression-free Survival (PFS) by Investigator Assessment | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using Lugano Classification | Up to approximately 3 years and 2.5 months | 
| PFS Event-Free Rate by Investigator Assessment | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for PFS at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| PFS by IRC Assessment | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an IRC using Lugano Classification | Up to approximately 3 years and 2.5 months | 
| PFS Event-Free Rate by IRC Assessment | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for PFS at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| Overall Survival (OS) | OS is defined as the time from first study drug administration to the date of death due to any cause | Up to approximately 3 years and 2.5 months | 
| OS Event-Free Rate | OS is defined as the time from first study drug administration to the date of death due to any cause. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for OS at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| Duration of Response (DOR) by Investigator Assessment | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using Lugano Classification. | Up to approximately 3 years and 2.5 months | 
| DOR Event-Free Rate by Investigator Assessment | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| DOR by IRC Assessment | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using Lugano Classification. | Up to approximately 3 years and 2.5 months | 
| DOR Event-Free Rate by IRC Assessment | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| Time to Treatment Failure (TTF) | TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason. | Up to approximately 3 years and 2.5 months | 
| TTF Event-Free Rate | TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for TTF at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| Time to Next Line of Therapy | Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL | Up to approximately 3 years and 2.5 months | 
| Time to Next Line of Therapy Event-Free Rate | Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for time to next line of therapy at 24 months with 95% confidence intervals estimated using Greenwood's formula. | Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported | 
| Time to Response (TTR) by Investigator Assessment | TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better) as assessed by the investigator using Lugano Classification | Up to approximately 3 years and 2.5 months | 
| TTR by IRC Assessment | TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by the IRC using Lugano Classification. | Up to approximately 3 years and 2.5 months | 
| Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS) | Mean change from baseline in EQ-5D-5L VAS. The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' Positive change from baseline indicates improved health. | Baseline to Cycle 30 (28 days per cycle) | 
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status | Mean change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Answers are converted to a score of 0 to 100, with a positive score from baseline indicating improved health. | Baseline to Cycle 30 (28 days per cycle) | 
| Number of Participants With Adverse Events | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs | From first dose to 30 days after last dose of study drug (Up to approximately 3 years and 2.5 months) | 
| Area Under the Curve From Time 0 to 6 Hours (AUC0-6) |  | Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle) | 
| Apparent Oral Clearance (CL/F) of Zanubrutinib |  | Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle) | 
| Maximum Observed Concentration (Cmax) |  | Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle) | 
| Elimination Half Life (t1/2) |  | Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGB-3111, Zanubrutinib