Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib

A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Bruton Tyrosine Kinase Inhibitor Zanubrutinib in Patients With CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The goal of this clinical trial was to evaluate whether zanubrutinib can effectively treat adults with CD79B-mutant relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Participants received zanubrutinib as monotherapy, underwent regular disease assessments to evaluate treatment response, and were monitored for safety and side effects throughout the study.

Study Overview

• Status: Completed
• Conditions: Relapsed Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Provincial Peoples Hospital Huifu Branch
    • Shantou, Guangdong, China, 515041
      • The First Affiliated Hospital of Shantou University Medical College
  • Hainan
    • Haikou, Hainan, China, 570312
      • Hainan Cancer Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310009
      • Zhejiang University College of Medicine Second Affiliated Hospital
    • Taizhou, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Participants had histologically confirmed diffuse large B-cell lymphoma, based on the World Health Organization 2008 classification of tumors of hematopoietic and lymphoid tissue.
2. Participants had a positive CD79B gene mutation, as confirmed by a central laboratory.
3. Participants had previously received at least one line of adequate systemic therapy for diffuse large B-cell lymphoma, defined as anti-CD20 antibody-based chemoimmunotherapy administered for at least two consecutive cycles, unless disease progression occurred before completion of Cycle 2.

4. Participants had relapsed or refractory disease prior to study entry, defined as either:

   1. Recurrent disease after achieving disease remission, defined as a complete response or partial response, at the completion of the most recent treatment regimen; or
   2. Stable disease or progressive disease at the completion of the most recent treatment regimen.

5. Participants were ineligible for high-dose therapy and stem cell transplantation, defined as meeting at least one of the following criteria:

   a. Presence of significant organ dysfunction, such as:

   1. Left ventricular ejection fraction less than 50 percent as measured by echocardiogram or multiple gated acquisition scan;
   2. Diffusing capacity of the lung for carbon monoxide less than 60 percent of the predicted value as measured by pulmonary function testing; or
   3. Creatinine clearance less than 70 milliliters per minute as demonstrated by nuclear medicine scan or 24-hour urine collection; or comorbid conditions that precluded the use of high-dose therapy and stem cell transplantation due to an unacceptable risk of treatment-related morbidity.

   b. Failure to achieve a complete response or partial response following salvage therapy.

   c. Failure to collect stem cells or inability to undergo stem cell collection, as assessed by the investigator.

Exclusion Criteria

1. Participants had non-Hodgkin lymphoma other than classical histology diffuse large B-cell lymphoma (not otherwise specified), including but not limited to:

   1. Diffuse large B-cell lymphoma transformed from indolent lymphomas
   2. Primary mediastinal (thymic) large B-cell lymphoma
   3. Primary cutaneous diffuse large B-cell lymphoma
   4. Primary effusion lymphoma
   5. Central nervous system lymphoma
2. Participants had a history of allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy.
3. Participants had prior exposure to a Bruton's tyrosine kinase inhibitor.

4. Participants had received any of the following treatments within the specified timeframe prior to the first dose of study drug:

   1. Corticosteroids administered with antineoplastic intent within two weeks prior to study treatment. A short course (seven days or fewer) of systemic corticosteroids at doses of 20 milligrams per day or less of prednisone equivalent for control of lymphoma-related symptoms was permitted prior to enrollment, provided the corticosteroids were tapered off within five days after initiation of study treatment.
   2. Chemotherapy or radiotherapy within two weeks.
   3. Monoclonal antibody therapy within two weeks.
   4. Investigational therapy within two weeks.
   5. Chinese patent medicine administered with antineoplastic intent within two weeks.

5. Participants had a history of other active malignancies within two years prior to study entry, with the exception of:

   1. Adequately treated carcinoma in situ of the cervix;
   2. Localized basal cell carcinoma or squamous cell carcinoma of the skin; or
   3. A previous malignancy that was confined and treated locally (by surgery or other modality) with curative intent.

Note: Other protocol-defined inclusion and exclusion criteria may have applied.

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; Participants received zanubrutinib 160 mg orally twice daily, administered continuously until disease progression, unacceptable toxicity, withdrawal of consent, initiation of alternative anticancer therapy, loss to follow-up, or study completion.	Drug: Zanubrutinib; Administered orally as capsules at a dose of 160 mg twice daily on a continuous dosing schedule.; Other Names: Brukinsa; BGB-3111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Defined as the percentage of participants who achieved complete response (CR) or partial response (PR) by investigator assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL).	Response was assessed every 12 weeks for the first 24 months and every 24 weeks thereafter. Maximum time on study was 36.4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CRR)	CRR was defined as the percentage of participants who achieved a complete response as their best overall response, as determined by investigator assessment according to the Lugano classification for NHL.	Response was assessed every 12 weeks for the first 24 months and every 24 weeks thereafter. Maximum time on study was 36.4 months
Duration of Response (DOR)	DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed to the date of first documented disease progression or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.	From the date of first documented response until to the data cutoff date (31MAR2025). Maximum time on study was 36.4 months
Progression-free Survival (PFS)	PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first as determined by investigator assessment according to the Lugano classification for NHL. Median PFS was estimated using the Kaplan-Meier method.	From first dose until the data cutoff date (31MAR2025). Maximum time on study was 36.4 months
Time to Response (TTR)	TRR was defined as the time from randomization to the first date that response criteria (CR or PR) were met, as determined by investigator assessment per the Lugano classification for NHL. Only participants who achieved an overall response were included in the analysis.	From first dose until disease progression or death, assessed up to the data cutoff date (31MAR2025). Maximum time on study was 36.4 months
Overall Survival (OS)	OS was defined as the time from randomization to the date of death from any cause. Median OS was estimated using the Kaplan-Meier method.	From first dose until the data cutoff date (31MAR2025). Maximum time on study was 36.4 months
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it was linked to the study drug.	From the first dose until 30 days after the last dose of zanubrutinib, death, or initiation of new anticancer therapy, whichever occurred first, assessed up to the data cutoff date (31MAR2025). Maximum treatment duration was 36.4 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Li Wang, Fei Li, Qingyuan Zhang, Hui Zhou, Ou Bai, Liping Su, Chunhong Hu, Zhiming Li, Kaiyang Ding, Qunyi Guo, Xiaoling Li, Xiaoxi Zhou, Wenjuan Yu, Shuhua Yi, Zhixia Wei, Wenbin Qian, Feiheng Chen, Guohui Cui, Zhiyu Liang, Qingchao Zeng, Jiaoyan Lyu, Yang Liu, Pan Zhang, Zhirong Shen, Zaixing Shi, Jing Rong, Keshu Zhou, Weili Zhao; BGB-3111-218: Single-arm, open-label, multicenter study of the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib (zanu) in patients with CD79B-mutated Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Blood 2025; 146 (Supplement 1): 3684. doi: https://doi.org/10.1182/blood-2025-3684

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-3111-218; CTR20210786 (Registry Identifier: ChinaDrugTrials)

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