Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Participants With B-cell Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety of zanubrutinib regimens in participants with B-cell malignancies who participated in a BeiGene parent study for zanubrutinib.

Official Title
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An Open-label, Multi-center, Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Patients With B-cell Malignancies

Conditions
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B-cell Malignancies

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Currently participating or participated recently in a BeiGene parent study Intent to continue or start zanubrutinib treatment after any of the following: At time of final analysis or study closure of the eligible BeiGene parent study At time of progressive disease (PD); and investigator, patient and medical monitor agree it is in the patient's best interest At an alternative timepoint for an alternative reason Patient who is currently on zanubrutinib treatment: Does not meet any protocol-specified criteria for zanubrutinib hold or permanent discontinuation, and, in the opinion of the investigator, will continue to benefit from zanubrutinib treatment Zanubrutinib-naive patient: Must meet the following criteria ≤ 15 days before first dose of study drug: Platelets ≥ 50,000/mm3 Absolute neutrophil count ≥ 750/mm3 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal Serum total bilirubin ≤ 3 x upper limit of normal (not required for Gilbert Syndrome) QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤ 480 msec No known New York Heart Association (NYHA) Class III or IV congestive heart failure Creatinine clearance ≥ 30 mL/min Female participants of childbearing potential and nonsterile males must be willing to use a highly effective method of birth control. Key Exclusion Criteria: Permanently discontinued from zanubrutinib treatment in the BeiGene parent study due to unacceptable toxicity, non-compliance with study procedures, or withdrawal of consent Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy Life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of zanubrutinib, or put the study outcomes at undue risk Concomitant chemotherapy, targeted therapy, radiation therapy, antibody-based therapies, or any prohibited concomitant therapy outlined in the protocol Pregnant or lactating woman Inability to comply with study procedures Concurrent participation in another therapeutic clinical study History of progressive disease (PD) while receiving a BTK inhibitor (excluding zanubrutinib) 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zanubrutinib (BGB-3111)<br>All participants to receive open-label zanubrutinib | Drug: Zanubrutinib<br>* Participants will receive zanubrutinib at a dose of 160 mg twice daily (for a total daily dose of 320 mg), or the last dose level received in the BeiGene parent study.<br>* Other names: BGB-3111;|
| Experimental: Zanubrutinib in combination with Tislelizumab<br>Participants to receive the combination as in the parent study (Australia Only) | Drug: Zanubrutinib<br>* Participants will receive zanubrutinib at a dose of 160 mg twice daily (for a total daily dose of 320 mg), or the last dose level received in the BeiGene parent study.<br>* Other names: BGB-3111;Drug: Tislelizumab<br>* Patients in Australia who participated in a parent study that involved combination therapy of zanubrutinib and tislelizumab will receive tislelizumab at a dose of 200mg every 3 weeks..<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | Safety as assessed by incidence of all treatment-emergent adverse events (TEAEs) and serious AEs (SAEs) | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) per investigator assessment | Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of first documentation of disease progression or death, whichever occurs first | Up to 5 years | 
| Duration of Response (DOR) per investigator assessment | Time from the date that response criteria are first met after the start of zanubrutinib in the eligible BeiGene study to the date that progressive disease (PD) is objectively documented or death, whichever occurs first | Up to 5 years | 
| Overall Survival (OS) | Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of death due to any reason | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zanubrutinib, Bruton's tyrosine kinase (BTK) inhibitor, long-term extension