Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment

A Phase 2, Multicenter, Single-arm Study of Zanubrutinib (BGB-3111) in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib

The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.

Study Overview

• Status: Completed
• Conditions: Waldenstrom Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80012-5405
      • Rocky Mountain Cancer Centers (Williams) Usor
  • Delaware
    • Newark, Delaware, United States, 19713-2055
      • Christiana Care
  • Florida
    • Fort Myers, Florida, United States, 33901-8108
      • SCRI Florida Cancer Specialists South
    • Jacksonville, Florida, United States, 32204-1128
      • St Century Oncology
    • St. Petersburg, Florida, United States, 33705-1449
      • SCRI Florida Cancer Specialists North
  • Illinois
    • Flossmoor, Illinois, United States, 60422-2067
      • Healthcare Research Network III, LLC
  • Minnesota
    • Burnsville, Minnesota, United States, 55337-6749
      • Minnesota Oncology Burnsville Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89169-3321
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Florham Park, New Jersey, United States, 07932-1049
      • Summit Medical Group
    • Morristown, New Jersey, United States, 07960-6136
      • Morristown Medical Center
  • New York
    • Westbury, New York, United States, 11590-5119
      • Clinical Research Alliance, Inc
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon Willamette Valley Cancer Center
  • Pennsylvania
    • Fountain Hill, Pennsylvania, United States, 18015-1153
      • St Lukes University Health Network
    • Horsham, Pennsylvania, United States, 19044-2331
      • Abington Hematology Oncology Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, Pllc Nashville
  • Texas
    • Amarillo, Texas, United States, 79106-1781
      • Texas Oncology Amarillo
    • Austin, Texas, United States, 78705-1163
      • Texas Oncology Tyler Longview
    • Dallas, Texas, United States, 75246-2079
      • Baylor Research Institute
    • McAllen, Texas, United States, 78503
      • Texas Oncology McAllen South Second Street
  • Virginia
    • Fairfax, Virginia, United States, 22031-4629
      • Us Oncology Virginia Cancer Specialists, Pc
    • Norfolk, Virginia, United States, 23502-2800
      • Virginia Oncology Associates
  • Washington
    • Seattle, Washington, United States, 98109-4433
      • Fred Hutchinson Cancer Research Center
    • Spokane, Washington, United States, 99208-1129
      • Medical Oncology Associates
  • Wisconsin
    • Madison, Wisconsin, United States, 53717-1959
      • Ssm Health Cancer Care Dean Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib

2. Ibrutinib and acalabrutinib intolerance is defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:

   1. For ibrutinib and acalabrutinib intolerance events:

      • 1 or more ≥ Grade 2 nonhematologic toxicities for >7 days (with or without treatment)
      • 1 or more ≥ Grade 3 nonhematologic toxicity of any duration
      • 1 or more Grade 3 neutropenia with infection or fever of any duration; or
      • Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression.

   2. For acalabrutinib intolerance events only;

      • 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with > 3 recurrent episodes; or
      • 1 or more ≥ Grade 1 nonhematologic toxicities for > 7 days (with or without treatment); or
      • Inability to use acid-reducing agents or anticoagulants (eg, proton pump inhibitors, warfarin) due to concurrent acalabrutinib use
3. Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤ Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1 acalabrutinib-related toxicities must have resolved to Grade 0 or baseline prior to initiating treatment with zanubrutinib.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
5. Absolute neutrophil count (ANC) ≥ 1000/mm^3 with or without growth factor support and platelet count ≥ 50,000/mm^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib

Key Exclusion Criteria:

1. Clinically significant cardiovascular disease including the following:

   1. Myocardial infarction within 6 months before the Screening
   2. Unstable angina within 3 months before the Screening
   3. New York Heart Association class III or IV congestive heart failure
   4. History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
   5. QT interval corrected by Fridericia's formula > 480 milliseconds
   6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
2. History of central nervous system (CNS) hemorrhage
3. Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
4. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL < 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, < 4 weeks before any Screening assessments are performed
5. Requires ongoing need for corticosteroid treatment > 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered.

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; Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib

Drug: Zanubrutinib; Zanubrutinib (BGB-3111) will be orally administered at a dose of 160 mg twice daily or 320mg once daily until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination.; Other Names: BGB-3111; BRUKINSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response as determined by investigator	24 months
Progression free survival (PFS) as determined by investigator	24 months
Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)	24 months
Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)	24 months
Disease control rate as determined by investigator	24 months

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• Shadman M, Flinn IW, Levy MY, Porter RF, Burke JM, Zafar SF, Misleh J, Kingsley EC, Yimer HA, Freeman B, Rao SS, Chaudhry A, Tumula PK, Gandhi MD, Manda S, Chen DY, By K, Xu L, Liu Y, Crescenzo R, Idoine A, Zhang X, Cohen A, Huang J, Sharman JP. Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. Lancet Haematol. 2023 Jan;10(1):e35-e45. doi: 10.1016/S2352-3026(22)00320-9. Epub 2022 Nov 16.
• Shadman M, Burke JM, Cultrera J, Yimer HA, Zafar SF, Misleh J, Rao SS, Farber CM, Cohen A, Yao H, Idoine A, An Q, Flinn IW, Sharman JP. Zanubrutinib is well tolerated and effective in patients with CLL/SLL intolerant of ibrutinib/acalabrutinib: updated results. Blood Adv. 2025 Aug 26;9(16):4100-4110. doi: 10.1182/bloodadvances.2024015493.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2019
• Primary Completion (Actual): January 9, 2026
• Study Completion (Actual): January 9, 2026

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: BTK Inhibitor; Zanubrutinib; BGB-3111; Ibrutinib Intolerance; Acalabrutinib Intolerance
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; 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-3111-215

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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