Clinical trial NCT03846427: Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma
Official title: A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
MZL
Keywords: BGB-3111
Zanubrutinib
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment
timeFrame: Up to approximately 3 years and 2.5 months
Secondary outcomes:
measure: ORR by Investigator Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)
timeFrame: Up to approximately 3 years and 2.5 months
measure: Progression-free Survival (PFS) by Investigator Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: PFS Event-Free Rate by Investigator Assessment
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: PFS by IRC Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: PFS Event-Free Rate by IRC Assessment
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years and 2.5 months
measure: OS Event-Free Rate
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: Duration of Response (DOR) by Investigator Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: DOR Event-Free Rate by Investigator Assessment
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: DOR by IRC Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: DOR Event-Free Rate by IRC Assessment
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: Time to Treatment Failure (TTF)
timeFrame: Up to approximately 3 years and 2.5 months
measure: TTF Event-Free Rate
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: Time to Next Line of Therapy
timeFrame: Up to approximately 3 years and 2.5 months
measure: Time to Next Line of Therapy Event-Free Rate
timeFrame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
measure: Time to Response (TTR) by Investigator Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: TTR by IRC Assessment
timeFrame: Up to approximately 3 years and 2.5 months
measure: Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS)
timeFrame: Baseline to Cycle 30 (28 days per cycle)
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status
timeFrame: Baseline to Cycle 30 (28 days per cycle)
measure: Number of Participants With Adverse Events
timeFrame: From first dose to 30 days after last dose of study drug (Up to approximately 3 years and 2.5 months)
measure: Area Under the Curve From Time 0 to 6 Hours (AUC0-6)
timeFrame: 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)
measure: Apparent Oral Clearance (CL/F) of Zanubrutinib
timeFrame: 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)
measure: Maximum Observed Concentration (Cmax)
timeFrame: 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)
measure: Elimination Half Life (t1/2)
timeFrame: 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)
Other outcomes:
Locations:
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Charlotte
country: United States
facility: The Charlotte Mecklenburg Hospital Authority
state: North Carolina
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: The Saint George Hospital Kogarah
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford PK
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Prague
country: Czechia
facility: University Hospital Vinohrady Hematology Department
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Marseille Cedex
country: France
facility: Hopital de La Conception Aphm
city: Paris
country: France
facility: Hopital Saint Louis
city: PierreBenite
country: France
facility: Chu Hopital Lyon Sud
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Modena
country: Italy
facility: Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
city: Terni
country: Italy
facility: Azienda Ospedaliera S Maria Di Terni
city: Torino
country: Italy
facility: Ao Citta Della Salute E Della Scienza Di Torino Presidio O
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Takapuna
country: New Zealand
facility: North Shore Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Greater Manchester
country: United Kingdom
facility: The Christie Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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.
citation: 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.
citation: 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.