Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

NCT03332173 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-3111-210CTR20170208
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 10

Brief Summary

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the Seventh International Workshop on Waldenström's Macroglobulinemia (IWWM). The study comprised an initial screening phase (up to 28 days), a single-arm treatment phase, and a follow-up phase.

Conditions

Waldenström's Macroglobulinemia (WM)

Outcome Measures

Primary Outcomes (1)

• Major Response Rate (MRR) as Assessed by the Independent Review Committee

  MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by an independent review committee according to modified Owen's criteria

  Up to approximately 1 year and 9 months

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  Up to approximately 1 year and 9 months

• PFS: Event-free Rate

  Up to approximately 1 year and 9 months

• Overall Response Rate (ORR)

  Up to approximately 1 year and 9 months

• Duration of Major Response (DOMR)

  Up to approximately 1 year and 9 months

• DOMR: Event-free Rate

  Up to approximately 1 year and 9 months

Study Arms (1)

Zanubrutinib

EXPERIMENTAL

Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

Oral administration using 80 mg capsules

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:

• Clinical and definitive histologic diagnosis of WM, meeting at least one criterion for treatment according to consensus panel criteria from the Seventh IWWM.
• WM pathology confirmation by central lab prior to study enrollment. Previous pathology report, concurrently with newly generated central lab report to be reviewed to support WM diagnosis.
• Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥ 2 continuous treatment cycles).
• Documented failure to achieve at least minor response or documented disease progression after response to the most recent treatment regimen.
• Neutrophils ≥ 0.75 x 10\^9/L independent of growth factor support within 7 days of first dose.
• Platelets ≥ 50 x 10\^9/L, independent of growth factor support or transfusion within 7 days of first dose.
• Hemoglobin ≥80 g/L, independent of erythropoietin (EPO) support or transfusion within 7 days of first dose of study drug.
• Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate \[eGFR\] from the Modification of Diet in Renal Disease \[MDRD\]).
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN).
• Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
• International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN. Participants with lupus anticoagulant or acquired von Willebrand disease due to WM may be enrolled after discussion with the medical monitor.
• ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥50%.
• Participants who relapse after autologous stem cell transplant may be enrolled if they are at least 6 months after transplant at screening. To be eligible after transplant, participants should have no active related infections.

You may not qualify if:

• Central nervous system (CNS) involvement by WM.
• Prior exposure to a BTK inhibitor.
• Evidence of disease transformation.
• Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, antineoplastic therapy with Chinese herbal medicine or antibody based therapies within 4 weeks of the start of study drug.
• Major surgery within 4 weeks of randomization.
• History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
• Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening.
• QTcF prolongation (defined as a QTc \>480 msecs based on Fridericia's formula) or other significant ECG abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block.
• Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Active infection including infections requiring oral or intravenous anti-microbial therapy.
• Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction \[PCR\]).
• Pregnant or lactating women.
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study at risk.
• On medications which are strong CYP3A inhibitors or strong CYP3A inducers.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (10)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510080, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital of Soochow University Branch Shizi

Suzhou, Jiangsu, 215006, China

Location

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

Related Publications (2)

• An G, Zhou D, Cheng S, Zhou K, Li J, Zhou J, Xie L, Jin J, Zhong L, Yan L, Guo H, Du C, Zhong J, Yu Y, Wu B, Qiu L. A Phase II Trial of the Bruton Tyrosine-Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Waldenstrom Macroglobulinemia. Clin Cancer Res. 2021 Oct 15;27(20):5492-5501. doi: 10.1158/1078-0432.CCR-21-0539. Epub 2021 Jul 12.

  PMID: 34253577 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

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; 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: November 2, 2017
• First Posted: November 6, 2017
• Study Start: August 31, 2017
• Primary Completion: May 8, 2019
• Study Completion: January 11, 2021
• Last Updated: October 26, 2024
• Results First Posted: March 8, 2022

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (10)