A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies
A Phase 1/1b Open-Label Dose-Escalation and Dose-Optimization Study of Bcl-2 Inhibitor BGB-21447 in Patients With Mature B-Cell Malignancies
4 other identifiers
interventional
112
4 countries
28
Brief Summary
This study is testing the safety and tolerability of BGB-21447 monotherapy in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aims to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), recommended Phase 2 dose (RP2D), and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study is divided into 2 main parts: Part 1 "Monotherapy Dose Finding" and Part 2 "Monotherapy Dose Optimization."
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2023
Typical duration for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2023
CompletedFirst Posted
Study publicly available on registry
April 25, 2023
CompletedStudy Start
First participant enrolled
June 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2026
CompletedMarch 12, 2026
March 1, 2026
2.9 years
April 12, 2023
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Part 1: Number of participants with dose limiting toxicities (DLTs)
Number of participants with dose limiting toxicities, as defined in the study protocol.
Up to approximately 1 month
Number of participants with adverse events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed and graded based upon the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months
Number of participants with Tumor Lysis Syndrome (TLS)
TLS will be determined via laboratory values and assessed by the investigator. In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the 24-hour period within 3 days before the start of study drug treatment or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months
Secondary Outcomes (15)
Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-21447
Up to approximately 8 weeks
Area under the curve from time 0 to the last sampling time point within the dose interval (AUC0-t) After a Single Dose of BGB-21447
Up to approximately 8 weeks
Area under the curve from time 0 extrapolated to infinity time (AUCinf) After a Single Dose of BGB-21447
Up to approximately 8 weeks
Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-21447
Up to approximately 8 weeks
Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-21447
Up to approximately 8 weeks
- +10 more secondary outcomes
Study Arms (4)
Part 1 (Cohort A1): Dose escalation in patients with B-cell non-Hodgkin lymphoma (NHL)
EXPERIMENTALParticipants with R/R B-cell NHL (including diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], marginal zone lymphoma \[MZL\], transformed B-cell NHL (B-NHL), and Richter's transformation to DLBCL) will receive BGB-21447 once a day.
Part 1 (Cohort B): Dose escalation in R/R CLL/SLL participants with low tumor burden
EXPERIMENTALParticipants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive BGB-21447 once a day.
Part 2 (Cohort A2.1): BGB-21447 Monotherapy Dose Optimization in R/R DLBCL
EXPERIMENTALParticipants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.
Part 2 (Cohort A2.2): BGB-21447 Monotherapy Dose Optimization in R/R FL or R/R MZL
EXPERIMENTALParticipants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.
Interventions
BGB-21447 will be administered orally
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis (per World Health Organization \[WHO\] guidelines, unless otherwise noted) of one of the following:
- Cohort A1 and Cohort A2:
- R/R DLBCL (for Cohort A1 and Cohort A2.1)
- High-grade B-cell lymphomas with translocations of MYC and Bcl-2 and/or Bcl-6 are not allowed in Cohort A1 but may be allowed in Cohort A2.1
- R/R FL (for Cohort A1 and Cohort A2.2)
- R/R MZL (for Cohort A1 and Cohort A2.2)
- Transformed B-cell NHL (for Cohort A1 only)
- Richter's transformation to DLBCL (for Cohort A1 only)
- Measurable disease by computed tomography/magnetic resonance imaging.
You may not qualify if:
- Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer or lentigo maligna melanoma that has been curatively resected
- Known central nervous system involvement by lymphoma/leukemia
- Prior autologous stem cell transplant \< 3 months before the first dose of study drug. Or prior chimeric antigen receptor T-cell (CAR-T) therapy \< 3 months before the first dose of study drug
- Prior allogeneic stem cell transplant.
- Major surgery \< 4 weeks before the first dose of study treatment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeOne Medicineslead
Study Sites (28)
Sibley Memorial Hospital Johns Hopkins Medicine
Washington D.C., District of Columbia, 20016, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242-1009, United States
Mission Cancer and Blood
Waukee, Iowa, 50263, United States
Sidney Kimmel Comprehensive Cancer At Johns Hopkins
Baltimore, Maryland, 21287, United States
Nyu Langone Health Perlmutter Cancer Center At Nyu Langone Hospital Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
New York, New York, 10016-2708, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105-2108, United States
Blacktown Cancer and Haematology Centre
Blacktown, New South Wales, NSW 2148, Australia
Pindara Private Hospital
Benowa, Queensland, QLD 4217, Australia
Mater Cancer Care Centre
South Brisbane, Queensland, QLD 4101, Australia
Monash Health
Clayton, Victoria, VIC 3168, Australia
Linear Clinical Research
Nedlands, Western Australia, WA 6009, Australia
Peking University Third Hospital
Beijing, Beijing Municipality, 100000, China
Fujian Cancer Hospital
Fuzhou, Fujian, 350014, China
Henan Cancer Hospital
Zhengzhou, Henan, 450000, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, 430030, China
Yichang Central Peoples Hospitaljiangnan Branch
Yichang, Hubei, 443001, China
The First Peoples Hospital of Changzhou
Changzhou, Jiangsu, 213000, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006, China
The First Affiliated Hospital of Nanchang University Branch Donghu
Nanchang, Jiangxi, 330006, China
The First Affiliated Hospital of Nanchang University Branch Xianghu
Nanchang, Jiangxi, 332000, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110004, China
Shandong Provincial Hospital
Jinan, Shandong, 250021, China
Linyi Peoples Hospital
Linyi, Shandong, 276000, China
Affiliated Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, 200032, China
Institute of Hematology and Hospital of Blood Disease
Tianjin, Tianjin Municipality, 300020, China
Auckland City Hospital
Auckland, 1023, New Zealand
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Director
BeOne Medicines
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2023
First Posted
April 25, 2023
Study Start
June 20, 2023
Primary Completion
May 1, 2026
Study Completion
May 1, 2026
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- See plan description
- Access Criteria
- See plan description
BeOne 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. BeOne 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 BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.