Zanubrutinib Plus Rituximab as Front-line Treatment for Mucosa-associated Lymphoid Tissue Lymphoma (MALT)

The purpose of this study is to evaluate the efficacy and safety of Zanubrutinib in combination with Rituximab as a first-line treatment for patients with mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.

Treatrment:

• Rituximab: 375 mg/m², administered once a week in Cycle 1 (C1) and on Day 1 (D1) of Cycles 2-6 (C2-C6).
• Zanubrutinib: 160 mg, administered twice daily from Day 1 to Day 28 (D1-D28). Each cycle lasts 28 days. After 6 cycles of treatment, patients who achieve complete remission (CR) will end treatment and enter observation follow-up. Patients with partial remission (PR) or stable disease (SD) will receive 2 additional cycles.

The primary study endpoint is the complete remission rate of Zanubrutinib in combination with Rituximab in the treatment of newly diagnosed mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.

Key inclusion Criteria:

• Mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma confirmed by histopathology.
• Newly diagnosed with Ann Arbor stage III-IV or relapsed MALT after local treatment .
• No prior systemic anti-lymphoma therapy (except for H. pylori eradication therapy in H. pylori-positive gastric MALT patients).
• No histopathological transformation to high-grade lymphoma.
• At least one measurable lesion according to the Lugano 2014 criteria.

• Age ≥ 18 years, with no gender restrictions. 7. An ECOG performance status score of 0-2. 8. An expected survival time of more than 12 months. 9. Adequate bone marrow, cardiac, pulmonary, liver, and kidney function. 10. Willing to participate in the clinical study; fully informed and aware of the study, having signed the informed consent form; willing and able to comply with all study procedures.

Key exclusion Criteria:

• Patients with a history of stroke, intracranial hemorrhage, or warfarin use within the past 6 months.
• Patients with central nervous system involvement.
• Patients who have undergone allogeneic hematopoietic stem cell transplantation in the past.
• Patients who have previously used BTK inhibitors or received CD20 monoclonal antibody therapy.

5, Patients with active infections, except for tumor-related B-symptom fever. 6. Patients with a concurrent history of other malignancies, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.

• Patients receiving potent cytochrome P450 inhibitors. 8. Patients with severe cardiovascular diseases, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or a history of myocardial infarction within the past 12 months.

• Patients, as judged by the investigator, who have significant organ dysfunction or uncontrollable comorbidities that pose a safety risk, or who have absorption and metabolism issues with Zanubrutinib.

• Pregnant or breastfeeding women and women of childbearing age unwilling to use contraception.

• Patients who have received anti-tumor therapy within 4 weeks prior to enrollment.

• Patients with active chronic hepatitis B or active hepatitis C. 13. Patients who have received systemic corticosteroid treatment or other immunosuppressive therapy within 14 days prior to the start of study treatment.