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

NCT03846427 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: BGB-3111-2142018-001284-24CTR20180823
• Study Type: interventional
• Target: 68
• Locations: 9 countries
• Sites: 31

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).

Conditions

Marginal Zone Lymphoma; MZL

Keywords

BGB-3111; Zanubrutinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• ORR by Investigator Assessment

  Up to approximately 3 years and 2.5 months

• ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)

  Up to approximately 3 years and 2.5 months

• Progression-free Survival (PFS) by Investigator Assessment

  Up to approximately 3 years and 2.5 months

• PFS Event-Free Rate by Investigator Assessment

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

• PFS by IRC Assessment

  Up to approximately 3 years and 2.5 months

Study Arms (1)

Zanubrutinib

EXPERIMENTAL

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

Interventions

Zanubrutinib DRUG

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

Also known as: BGB-3111, Brukinsa

Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes
• 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
• Current need for systemic therapy for MZL
• Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) of 0-2
• Life expectancy ≥ 6 months
• Adequate bone marrow function
• Adequate organ function
• Male and female participants must use highly effective methods of contraception

You may not qualify if:

• Known transformation to aggressive lymphoma, eg, large cell lymphoma
• Clinically significant cardiovascular disease
• 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
• 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
• History of stroke or intracranial hemorrhage
• Severe or debilitating pulmonary disease
• Active fungal, bacterial and/or viral infection requiring systemic therapy
• Known central nervous system involvement by lymphoma
• Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection
• Major surgery within 4 weeks of the first dose of study drug
• Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor
• Pregnant or lactating women
• Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer
• Concurrent participation in another therapeutic clinical trial

Sponsors & Collaborators

• BeiGene: lead

Study Sites (31)

Clinical Research Alliance, Inc

Westbury, New York, 11590, United States

Location

The Charlotte Mecklenburg Hospital Authority

Charlotte, North Carolina, 28203, United States

Location

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

The Saint George Hospital Kogarah

Kogarah, New South Wales, 2217, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford PK, South Australia, 5042, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peninsula Private Hospital

Frankston, Victoria, 3199, Australia

Location

Peking University Third Hospital

Beijing, Beijing Municipality, 100000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, 300020, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

University Hospital Vinohrady Hematology Department

Prague, 10034, Czechia

Location

Centre de Lutte Contre Le Cancer Institut Bergonie

Bordeaux, 33076, France

Location

Hopital de La Conception Aphm

Marseille, 13005, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Chu Hopital Lyon Sud

PierreBenite, 69495, France

Location

Policlinico Sorsola Malpighi, Aou Di Bologna

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco

Modena, 41124, Italy

Location

Azienda Ospedaliera S Maria Di Terni

Terni, 05100, Italy

Location

Ao Citta Della Salute E Della Scienza Di Torino Presidio O

Torino, 10126, Italy

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

North Shore Hospital

Takapuna, 0622, New Zealand

Location

Severance Hospital Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Christie Hospital

Greater Manchester, M20 4BX, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (6)

• 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

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 34526366 BACKGROUND

• 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.

  BACKGROUND

• Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.

  PMID: 38502198 DERIVED

• Opat S, Tedeschi A, Hu B, Linton KM, McKay P, Leitch S, Coleman M, Zinzani PL, Jin J, Sun M, Sobieraj-Teague M, Browett P, Ke X, Thieblemont C, Ardeshna K, Bijou F, Walker P, Hawkes EA, Ho SJ, Zhou K, Liang Z, Xu J, Tankersley C, Delarue R, Co M, Trotman J. Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study. Blood Adv. 2023 Nov 28;7(22):6801-6811. doi: 10.1182/bloodadvances.2023010668.

  PMID: 37682792 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: February 19, 2019
• Study Start: February 19, 2019
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: October 26, 2024
• Results First Posted: March 3, 2022

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (4); FR (4); AU (8); KR (1); IT (5); GB (4); US (2); CZ (1); NZ (2)