Optimize Study - Orelabrutinib Combined With BR/G in Untreated Marginal Zone Lymphoma (MZL)

Inclusion Criteria:

1. For Cohort A: Age 18-70 years, physical condition assessed by a physician assuitable for chemotherapy; for Cohort B: Age 70 or older or under 70 years of ageassessed by a physician as unsuitable for chemotherapy.

2. Gender is not limited.

3. Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL.

4. Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment,hepatitis C treatment).

5. ECOG performance score 0-3 points (if the score is 3 points, the physician needs toassess that the deterioration of physical condition is mainly due to tumor burden).

6. Indications for treatment (with B symptoms, blood cell decline, bleeding, largemass, rapid progression of tumors, etc.).

7. Major organ functions meet the following criteria: a) Complete blood count: Absoluteneutrophil count ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥75g/L; ifaccompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10^9/L,platelets ≥50×10^9/L, hemoglobin ≥50g/L. b) Blood biochemistry: Total bilirubin ≤1.5times the upper limit of normal (ULN), AST or ALT ≤2 times ULN; serum creatinine ≤1.5 times ULN; serum amylase ≤ULN. c) Coagulation function: Internationalnormalized ratio (INR) ≤1.5 times ULN.

8. Life expectancy ≥3 months.

9. Voluntarily sign a written informed consent form before the trial screening.

Exclusion Criteria:

1. Currently or previously have other malignant tumors, unless radical treatment hasbeen performed and there is evidence of no recurrence or metastasis within the last 5 years.

2. Lymphoma involving the central nervous system or transformation to a higher grade.

3. Have uncontrollable or significant cardiovascular diseases, including: a) Within 6months before the first administration of the study drug, there is a history of NewYork Heart Association (NYHA) class II or above congestive heart failure, unstableangina, myocardial infarction, or arrhythmias requiring treatment at the time ofscreening, with a left ventricular ejection fraction (LVEF) <50%. b) Primarycardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy,arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy,unclassified cardiomyopathy). c) A history of clinically significant QTc intervalprolongation, or a QTc interval >470ms in females and >450ms in males duringthe screening period. d) Symptomatic or medication-requiring coronary artery heartdisease subjects. e) Subjects with uncontrollable hypertension (despite lifestyleimprovements and the use of reasonable, tolerable, and adequate doses of three ormore antihypertensive drugs, including diuretics, for more than 1 month, bloodpressure is still not at the standard, or it is only effectively controlled whentaking four or more antihypertensive drugs).

4. Active bleeding within 2 months before screening, or currently taking anticoagulantdrugs, or the investigator believes there is a clear bleeding tendency.

5. History of deep vein thrombosis or pulmonary embolism within the past six months.

6. Clinically significant gastrointestinal abnormalities that may affect the intake,transport, or absorption of drugs (such as inability to swallow, chronic diarrhea,intestinal obstruction), or subjects who have undergone total gastrectomy.

7. History of organ transplantation or allogeneic bone marrow transplantation.

8. Major surgery within 6 weeks before screening or minor surgery within 2 weeks beforescreening. Major surgery is surgery that uses general anesthesia, but endoscopicexaminations for diagnostic purposes are not considered major surgery. Insertion ofvascular access devices will be exempt from this exclusion criterion.

9. Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb with positiveHBV DNA titer), positive for HCV Ab, HIV/AIDS, or other serious infectious diseases;define active infection.

10. Subjects currently with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis,radiation pneumonitis, drug-related pneumonia, etc., that seriously affect lungfunction.

11. Previously treated with BTK, BCR pathway inhibitors (such as PI3K, Syk), and BCL-2inhibitors.

12. Pregnant, breastfeeding women, and subjects of childbearing age who are unwilling totake contraceptive measures.

13. Need to continuously take drugs with moderate to severe inhibitory effects oncytochrome P450 CYP3A or strong inductive effects.

14. Other situations deemed unsuitable for participating in this trial by theinvestigator.