Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study was to evaluate the efficacy of zanubrutinib in participants with centrally confirmed relapsed or refractory MCL.

Official Title
-----------------
A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Efficacy and Safety of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Conditions
-----------------
Refractory Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Zanubrutinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Diagnostic report had to include evidence for morphological and cyclin D1 or t (11; 14). Eastern Cooperative Oncology Group performance status of 0-2. Measurable disease by computed tomography/magnetic resonance imaging. Received prior regimens for MCL. Documented failure to achieve any response, (stable disease or progressive disease during treatment) or documented progressive disease after response to the most recent treatment regimen. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN). Total bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome). Life expectancy of > 4 months. Key Exclusion Criteria: Current or history of central nervous system lymphoma. Prior exposure to a BTK inhibitor before enrollment. Prior corticosteroids with anti-neoplastic intent within 7 days. Major surgery within 4 weeks of screening. Toxicity must have recovered from prior chemotherapy. History of other active malignancies within 2 years of study entry. Currently clinically significant active cardiovascular disease. QT interval corrected with Fridericia's formula > 450 microseconds or other significant electrocardiogram abnormalities. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy. Known human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction). Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 milligrams) administered orally twice daily | Drug: Zanubrutinib<br>* Administered as specified in the treatment arm.<br>* Other names: BGB-3111;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) As Assessed By Independent Review Committee | The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. | Up to 1 year and 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated. | Up to 3 years and 6 months | 
| Time To Response | Time to response was defined as the time from treatment initiation to the first documentation of response. | Up to 3 years and 6 months | 
| Duration Of Response | The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment. | Up to 3 years and 6 months | 
| ORR As Assessed By The Investigator | The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR. | Up to 3 years and 6 months | 
| Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first. | From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months) | 
| Number Of Participants Experiencing AEs Leading To Treatment Discontinuation | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months) |