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

BeiGene68 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Marginal Zone Lymphoma MZL

Interventions

ZanubrutinibDRUG

Zanubrutinib at a dose of 160 mg orally twice a day (BID)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Age 18 years or older 2. Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes 3. 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 4. Current need for systemic therapy for MZL 5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) 6. Eastern Cooperative Oncology Group (ECOG) of 0-2 7. Life expectancy ≥ 6 months 8. Adequate bone marrow function 9. Adequate organ function 10. Male and female participants must use highly effective methods of contraception Key Exclusion Criteria: 1. Known transformation to aggressive lymphoma, eg, large cell lymphoma 2. Clinically significant cardiovascular disease 3. 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 4. 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 5. History of stroke or intracranial hemorrhage 6. Severe or debilitating pulmonary disease 7. Active fungal, bacterial and/or viral infection requiring systemic therapy 8. Known central nervous system involvement by lymphoma 9. Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection 10. Major surgery within 4 weeks of the first dose of study drug 11. Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor 12. Pregnant or lactating women 13. Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer 14. Concurrent participation in another therapeutic clinical trial NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (31)

Outcomes

Primary Outcomes

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

Time frame: Up to approximately 3 years and 2.5 months

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

Data from ClinicalTrials.gov

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Clinical Research Alliance, Inc

Westbury, New York, United States

The Charlotte Mecklenburg Hospital Authority

Charlotte, North Carolina, United States

Canberra Hospital

Garran, Australian Capital Territory, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

The Saint George Hospital Kogarah

Kogarah, New South Wales, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Flinders Medical Centre

Bedford PK, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Monash Health

Clayton, Victoria, Australia

Peninsula Private Hospital

Frankston, Victoria, Australia

...and 21 more locations

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

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

Duration of Response (DOR) by Investigator Assessment

Time frame: 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.

Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

DOR by IRC Assessment

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)