Zanubrutinib for Chinese adults with newly diagnosed 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

This study will test zanubrutinib in Chinese adults with newly diagnosed (treatment‑naive) Waldenström macroglobulinemia to see if it works and is safe.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BeOne Medicines (Industry-sponsored)
• Drugs / interventions: zanubrutinib, chemotherapy, radiation
• Locations: 8 sites (Beijing, Beijing Municipality and 7 other locations)
• Trial ID: NCT07169331 on ClinicalTrials.gov

What this trial studies

This Phase 4, multi‑center interventional study gives zanubrutinib to Chinese adults with treatment‑naive Waldenström macroglobulinemia and systematically collects efficacy and safety data to meet post‑marketing requirements from the NMPA. Eligible participants must have measurable disease (serum IgM > 0.5 g/dL), meet IWWM treatment criteria, and have ECOG performance status 0–2 with adequate organ function. The study is being conducted at major cancer centers in mainland China and will follow participants while recording response rates and adverse events. Results will further characterize how well zanubrutinib controls disease and its tolerability in this specific population.

Who should consider this trial

Good fit: Ideal candidates are Chinese adults with newly diagnosed (treatment‑naive) Waldenström macroglobulinemia who meet IWWM treatment criteria, have measurable disease (IgM > 0.5 g/dL), ECOG 0–2, and adequate organ function.

Not a fit: Patients who have received prior systemic therapy for WM, those with poor organ function (for example creatinine clearance < 30 ml/min), very low blood counts, or who do not meet the IWWM criteria for treatment may not receive benefit from participation.

Why it matters

Potential benefit: If successful, the study could confirm zanubrutinib as an effective and tolerable oral treatment option for Chinese patients with newly diagnosed Waldenström macroglobulinemia.

How similar studies have performed: Other trials of zanubrutinib and other BTK inhibitors have shown meaningful responses in Waldenström macroglobulinemia, and this study extends that experience to a Chinese treatment‑naive population for post‑marketing characterization.

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:

  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

Where this trial is running

Beijing, Beijing Municipality and 7 other locations

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

Study contacts

• Study coordinator: Study Director

Conditions Waldenström's Macroglobulinemia