Combining Orelabrutinib and Zuberitamab for treating Marginal Zone Lymphoma

Inclusion Criteria:

1\. Age 18 years or older; 2. ECOG performance status (PS) level 0\~2; 3. The expected survival is not less than 12 weeks; 4. CD20-positive marginal area lymphoma confirmed according to WHO2008 lymphoma classification standard, including splenic MZL, lymph node MZL and extranodal MZL subtypes; 5. MZL with stage III/IV disease and stage I/II disease recurrence or progression after local treatment can also be included, and patients who have received BTKi inhibitor therapy for more than 6 months can also be included; 6. Enhanced computerized tomography/magnetic resonance imaging (CT/MRI) to detect measurable lesions; 7. Indications for MZL treatment that meet NCCN guidelines and have not received systematic treatment for MZL in the past (anti-infective treatment such as anti-HP and HCV is not systemic treatment); 8. The main organ function is normal and meet the following criteria :

1. blood routine examination standards must meet:

   1. ANC\>1.0×109/L;
   2. PLT\>75×109/L (≥50×109/L for patients with confirmed bone marrow infiltration);
   3. Hb\>80g/dL;
2. Biochemical examination should meet the following criteria :

   1. TBIL\<2×ULN;
   2. ALT and AST\<2.5XULN(for patients with liver invasion,ALT and AST\<5×ULN);
   3. Endogenous creatinine clearance ≥40ml/min (Cockcroft-Gault formula). 9. Women of childbearing age must have been using reliable contraception or had a pregnancy test (serum or urine) within 7 days of enrol with a negative result and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last dose of the test drug. For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and 8 weeks after the last dose of the trial drug; 10. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

      \-

      Exclusion Criteria:
      1. Patients with central nervous system invasion;
      2. Previous or co-existing uncured malignancies, except cured skin basal cell MZL clinical trial protocol cancer, cervical carcinoma in situ and superficial bladder cancer;
      3. Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval 2450 ms for men and 2470 ms for women); According to NYHA standards, patients with grade III to V cardiac insufficiency or left ventricular ejection fraction (LVEF) \<50% indicated by cardiac color ultrasound;
      4. Abnormal coagulation function (INR\>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), have a tendency to hemorrhage or are receiving thrombolytic or anticoagulant therapy;
      5. Arteriovenous thrombosis events occurring in the 12 months prior to enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
      6. The presence of known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliac, coagulation disorder, thrombocytopenia, hypersplenism, etc.);
      7. Had major surgery or severe traumatic injury, fracture or ulcer within 4 weeks of enrollment;
      8. Have significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
      9. Active infections that require antimicrobial treatment (such as antimicrobial drugs, antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment, antifungal drug treatment);
      10. Active hepatitis B (HBV DNA\>2000IU/mL or 104 copy numbers /mL) or hepatitis C (hepatitis C antibody positive with HCVRNA higher than the lower detection limit of analytical methods);
      11. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
      12. Had participated in other anti-tumor drug clinical trials within 4 weeks before enrollment;
      13. Patients who had received potent CYP3A4 inhibitors within 7 days before enrollment, or had received potent CYP3A4 inducers within 12MZL clinical trial regimen days before enrollment;
      14. Pregnant or lactating women; A fertile patient who is unwilling or unable to take effective contraceptive measures;
      15. The investigator determines other circumstances that may affect the conduct of the clinical study and the determination of the study results.