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

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

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.

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:

  1. 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.

  2. Creatinine clearance of ≥ 30 ml/min as estimated by the Cockcroft-Gault formula.

  3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN).

  4. 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:

  1. Active cardiac ischemia (eg, cardiac chest pain) ≤ 28 days before first dose of study drug.
  2. Any history of acute myocardial infarction ≤ 6 months before the first dose of study drug.
  3. 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.
  4. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drug.
  5. Active, clinically significant second-degree atrioventricular block Mobitz II, or third degree atrioventricular block.
  6. Any history of cerebrovascular accident ≤ 6 months before the first dose of study drug.
  7. Uncontrolled hypertension that cannot be managed by standard antihypertension medications ≤ 28 days before the first dose of study drug.
  8. 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