A Study to Evaluate the Efficacy and Safety of Zanubrutinib in Chinese Adults With Treatment-Naive Waldenström Macroglobulinemia

Official title

A Phase 4, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Zanubrutinib in Chinese Patients With Treatment-Naive Waldenström Macroglobulinemia

Overview

The purpose of this study is to measure the efficacy and safety with zanubrutinib in adults with Treatment-Naive (TN) Waldenström Macroglobulinemia (WM). The main objective of this Phase 4 study is to further characterize the efficacy of zanubrutinib in Chinese participants with TN WM in order to fulfill the post-marketing requirements from the National Medical Products Administration (NMPA). Safety data will be collected and evaluated in this study as well.

Interventions

• Drug Zanubrutinib
  Administered orally

Primary outcome measures

• Percentage of Participants Achieving a Complete Response (CR) or Very Good Partial Response (VGPR) as Assessed by the Investigator [Time frame: Up to approximately 33 Months]

Secondary outcome measures (4)

• Major Response Rate (MRR) as Assessed by the Investigator [Time frame: Up to approximately 33 Months]
• Duration of Major Response (DOMR) as Assessed by the Investigator [Time frame: Up to approximately 33 Months]
• Progression-free Survival (PFS) as Assessed by the Investigator [Time frame: Up to approximately 33 Months]
• Number of Participant with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From first dose of study drug until 30 days after the last dose, up to approximately 33 months]

Eligibility criteria

Inclusion criteria

• Clinical and definitive histologic diagnosis of WM. Participant must be treatment-naive.
• Participant must meet at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's macroglobulinemia (IWWM).
• Participant must have measurable disease, as defined by serum immunoglobulin M (IgM) level > 0.5 g/dL.
• Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Participants must have adequate organ function as indicated by the following laboratory values ≤ 7 days before the first dose of study treatment:

• Participants must not have required blood transfusion or growth factor support ≤ 7 days before sample collection at screening for the following:

• Absolute neutrophil count (ANC) ≥ 0.75 x 10\^9/L.
• Platelets ≥ 50 x 10\^9/L.
• Creatinine clearance of ≥ 30 ml/min as estimated by the Cockcroft-Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN).
• Serum total bilirubin ≤ 2 x ULN (total bilirubin must be < 3 x ULN for participants with Gilbert syndrome).
• Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for at least 1 month after the last dose of zanubrutinib. They must also have a negative urine or serum pregnancy test result ≤ 7 days before the first dose of study treatment.

Exclusion criteria

• Evidence of disease transformation at the time of study entry.
• Central nervous system (CNS) involvement by WM. Patients with a history of CNS involvement must undergo magnetic resonance imaging (MRI) and cerebrospinal fluid cytology studies to document no evidence of CNS disease prior to study entry.
• Evidence of disease transformation at the time of study entry.
• Participants with any of the following cardiovascular risk factors:

• Active cardiac ischemia (eg, cardiac chest pain) ≤ 28 days before first dose of study drug.
• Any history of acute myocardial infarction ≤ 6 months before the first dose of study drug.
• Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (Appendix 7)≤ 6 months before the first dose of study drug.
• Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drug.
• Active, clinically significant second-degree atrioventricular block Mobitz II, or third degree atrioventricular block.
• Any history of cerebrovascular accident ≤ 6 months before the first dose of study drug.
• Uncontrolled hypertension that cannot be managed by standard antihypertension medications ≤ 28 days before the first dose of study drug.
• Any episode of syncope or seizure ≤ 28 days before first dose of study drug.
• At the time of study entry, participants taking warfarin or other vitamin K antagonists.
• Participants requiring ongoing therapy with strong or moderate cytochrome CYP3A inducers
• Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy, targeted therapy, or radiation therapy within 4 weeks, or antibody-based therapy within 4 weeks before the start of study drug.
• Major surgical procedure within 4 weeks before the start of study treatment (bone marrow aspirate and biopsy procedures are not considered major surgical procedures).

Note: Other protocol defined criteria may apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 8 centers

• Peking Union Medical College Hospital — Beijing
• Sun Yat Sen University Cancer Center — Guangzhou
• Nanfang Hospital, Southern Medical University — Guangzhou
• Affiliated Hospital of Hebei University — Baoding
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Yichang Central Peoples Hospital — Yichang
• Xiangya Hospital of Central South University — Changsha
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07169331 · BGB-3111-404

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗