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

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

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 Overview

• Status: Completed
• Conditions: Marginal Zone Lymphoma; MZL
• Intervention / Treatment: Drug: Zanubrutinib

Detailed Description

This is a Phase 2, open-label study of zanubrutinib in approximately 65 participants with R/R MZL. The study will evaluate efficacy, as measured by overall response rate, safety and tolerability.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Kogarah, New South Wales, Australia, 2217
      • The Saint George Hospital Kogarah
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford PK, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Frankston, Victoria, Australia, 3199
      • Peninsula Private Hospital
• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
• Czechia
  • Prague, Czechia, 10034
    • University Hospital Vinohrady Hematology Department
• France
  • Bordeaux, France, 33076
    • Centre de Lutte Contre Le Cancer Institut Bergonie
  • Marseille Cedex, France, 13005
    • Hopital de la Conception APHM
  • Paris, France, 75010
    • Hopital Saint Louis
  • PierreBenite, France, 69495
    • Chu Hopital Lyon Sud
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sorsola Malpighi, Aou Di Bologna
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41124
    • Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
  • Terni, Italy, 05100
    • Azienda Ospedaliera S Maria Di Terni
  • Torino, Italy, 10126
    • Ao Citta Della Salute E Della Scienza Di Torino Presidio O
• Korea, Republic of
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Severance Hospital Yonsei University Health System
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Takapuna, New Zealand, 0622
    • North Shore Hospital
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Greater Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • London, United Kingdom, NW1 2PG
    • University College Hospital
• United States
  • New York
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance, Inc
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • The Charlotte Mecklenburg Hospital Authority

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib; 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; Zanubrutinib at a dose of 160 mg orally twice a day (BID); Other Names: Brukinsa; BGB-3111

What is the study measuring?

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
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)
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)
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)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, BeiGene

Publications and helpful links

General Publications

• Stephen Opat, Robert Marcus, MA, FRCP, FRCPath, Craig A. Portell, MD, William Reed, MD, Chris Tankersley, Jane Huang, MD, Judith Trotman, MBChB, FRACP, FRCPA. Phase 2 Study of Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Marginal Zone Lymphoma. Blood. 2019; 134(1):5256. https://doi.org/10.1182/blood-2019-122629
• Stephen Opat, et al. Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Initial Results of the MAGNOLIA (BGB-3111-214) Trial. Presented at the 62nd American Society of Hematology (ASH) Annual Meeting, December 5-8, 2020. Abstract 339.
• Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. doi: 10.1158/1078-0432.CCR-21-1704. Epub 2021 Sep 15.
• Opat S, Tedeschi A, Hu B, et al: Long-term efficacy and safety of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma. 2022 ASH Annual Meeting and Exposition. Abstract 234. Presented December 10, 2022.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2019
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: February 15, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Zanubrutinib; BGB-3111
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, B-Cell, Marginal Zone; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: BGB-3111-214; 2018-001284-24 (EudraCT Number); CTR20180823 (Registry Identifier: Center for drug evaluation, CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No