Phase 3
Completed N=201
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
Source: ClinicalTrials.gov NCT03053440 ↗Enrolled (actual)
201
Serious AEs
54.8%
Results posted
Jun 2023
Primary outcomePrimary: Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC) — 19.2; 28.4 Percentage of Participants — p=0.0921
◆ Published Evidence
Established
38citations · ~5 / year
A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia.
Summary
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
Linked Publications (5)
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A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia.
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Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib.
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Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia.
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Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial.
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Outcomes after transition from ibrutinib to zanubrutinib in patients with Waldenström macroglobulinemia from the ASPEN study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC) |
19.2; 28.4 | 0.0921 |
| SECONDARY Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC |
77.8; 77.5 | — |
| SECONDARY Duration of Response (DOR) as Assessed by IRC |
NA; NA | — |
| SECONDARY DOR as Assessed by IRC: Event -Free Rate |
87.9; 94.4; 87.9; 85.2 | — |
| SECONDARY Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator |
25.3; 38.2 | — |
| SECONDARY DOR as Assessed by the Investigator |
NA; NA | — |
| SECONDARY DOR as Assessed by the Investigator: Event-Free Rate |
87.7; 89.7; 77.5; 81.1; 73.9; 81.1 | — |
| SECONDARY Progression Free Survival (PFS) as Assessed by the IRC |
NA; NA | — |
| SECONDARY PFS as Assessed by IRC: Event-Free Rate |
87.2; 89.7; 83.8; 85.0 | — |
| SECONDARY PFS as Assessed by the Investigator |
NA; NA | — |
| SECONDARY PFS as Assessed by the Investigator: Event-Free Rate |
80.6; 88.5; 74.8; 78.3; 67.3; 78.3 | — |
| SECONDARY Percentage of Participants With Resolution of All Treatment-precipitating Symptoms |
78.6; 79.2 | — |
| SECONDARY Percentage of Participants With an Anti-Lymphoma Effect |
84.2; 78.8 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
98; 101; 50; 59 | — |
Eligibility Criteria
Key Inclusion Criteria
- Clinical and definitive histologic diagnosis of WM
- Measurable disease, requiring treatment
- Participants with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen
- Age ≥ 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate bone marrow function
- Adequate renal and hepatic function
- Electrocardiogram/multigated acquisition scan (ECHO/MUGA) demonstrating left ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal
- Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 3 months after transplant, and after allogeneic transplant if they are at least 6 months post-transplant.
- Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Males must have undergone sterilization- vasectomy, or utilize a barrier method
- Life expectancy of > 4 months
Key Exclusion Criteria
- Prior exposure to a BTK inhibitor
- Evidence of disease transformation at the time of study entry
- Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy given with antineoplastic intent, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug
- Major surgery within 4 weeks of study treatment
- Toxicity of ≥ Grade 2 from prior anticancer therapy
- 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 with curative intent
- Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease within 6 months of screening
- QTcF prolongation (defined as a QTcF > 480 msec)
- Active, clinically significant Electrocardiogram (ECG) abnormalities
- 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
- Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy
- Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C
- Pregnant or lactating women
- Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the subject's safety
- Any medications which are strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT03053440) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.