IBI376 Plus Rituximab in Patients With Untreated Indolent Lymphoma.

Inclusion Criteria:

1. Age ≥ 18 years old, male or female;
2. Grade 1-3a follicular lymphoma or marginal zone lymphoma derived from B cells was confirmed by pathology;
3. Immunohistochemistry showed CD20 positive;
4. Have not received systemic anti-tumor therapy in the past;
5. Lugano stage is stage III-IV (Note: 2014 Lugano stage is adopted for non gastric or intranodal marginal zone lymphoma, and Lugano modified version of Ann Arbor stage system is adopted for gastrointestinal marginal zone lymphoma);
6. Patients with Lugano stage I-II and recurrence only after radiotherapy can be included in the group;
7. For subjects who relapsed only after radiotherapy, radiotherapy was completed 12 weeks before the first application of IBI376;
8. Patients with Helicobacter pylori (HP) - positive mucosa associated lymphoid tissue lymphoma (MALT) can be enrolled if their pathological tissue type has not changed after failure of anti HP treatment;
9. Any tumor load with treatment indications and one of the following is met:

   1. Have any discomfort symptoms that affect normal work and life;
   2. The function of end organs was impaired;
   3. Hemocytopenia secondary to lymphoma invading bone marrow;
   4. Massive lesions;
   5. Sustained or rapid progression
10. The presence of evaluable target lesions is defined as the presence of ≥ 1 lesion with the longest diameter (LD) measurement \> 1.5cm and the longest vertical longitude (LPD) measurement ≥ 1.0cm assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with splenic marginal zone lymphoma (SMZL) can be enrolled if there is no measurable target lesion, but there is a clear basis for lymphoma bone marrow infiltration (bone marrow smear, biopsy or flow cytometry);
11. Eastern Cooperative Oncology Group（ECOG） physical fitness status is 0-2 points;
12. Life expectancy ≥ 12 weeks;
13. Subjects must be willing to undergo incision, resection or coarse needle lymph node or tissue biopsy, or provide lymph node or tissue biopsy of recently available archived tissue (at least 10 white films) for pathological review in the research center;
14. Willing to use contraception according to the following criteria:

    1. Women of childbearing age (15 \~ 49 years old) must undergo pregnancy test within 7 days before starting treatment, and the result is negative;
    2. Women of childbearing age shall take effective contraceptive measures at least 120 days after the last administration of the study drug (the contraceptive success rate shall be at least 99%). The available methods with contraceptive success rate of at least 99% shall be communicated with the subjects and confirmed;
    3. Male subjects took effective contraceptive measures at least 93 days after the last administration of the study drug (the contraceptive success rate was at least 99%). The available methods with a contraceptive success rate of at least 99% shall be communicated with the subjects and confirmed;
    4. Infertile women (i.e. sterilized by hysterectomy and / or bilateral oophorectomy or amenorrhea ≥ 12 months and age \> 45 years) are not subject to the above conditions a and b;
15. Have sufficient bone marrow and organ functions (do not use growth factors to obtain normal values. Subjects with hemocytopenia caused by lymphoma bone marrow invasion are not subject to the following conditions a, b and c):

    1. Neutrophil count (ANC) ≥ 1.0 × 10\^9/L；
    2. Hemoglobin ≥ 8.0g/dl;
    3. Platelet count ≥ 50 × 10\^9/L；
    4. Total bilirubin ≤ 1.5 × The upper limit of normal value (ULN), Gilbert syndrome, cholestasis caused by hilar compression adenosis, biliary obstruction caused by liver involvement or lymphoma \< 3 times ULN;
    5. Alanine aminotransferase / aspartate aminotransferase (ALT / AST) ≤ 2.5 × ULN or ≤ 5 × ULN (in the presence of liver invasion);
    6. Creatinine clearance calculated by Cockcroft Gault equation ≥ 40ml / min or glomerular filtration rate estimated by diet modified formula for renal disease ≥ 40ml / min / 1.73m\^2;
    7. Lipase ≤ 1.5 × ULN.

Exclusion Criteria:

1. Transformation from inert non-Hodgkin lymphoma to diffuse large B-cell lymphoma is known;
2. Lymphoma involving the central nervous system;
3. Known human immunodeficiency virus (HIV) infection or positive immunoassay;
4. Viral infections that cannot be controlled by antiviral drugs, such as herpes virus infection, acute or chronic active hepatitis B, acute or chronic active hepatitis C, etc \[Note: chronic Hepatitis B virus (HBV) carriers or inactive hepatitis B surface antigen (HBsAg) positive subjects can be enrolled, and HBV-DNA is lower than the lower limit of detection; hepatitis C virus (HCV) antibody negative patients can be enrolled, HCV antibody positive patients need to be tested for HCV-RNA, and if they are negative, they can be enrolled\];
5. There are active infectious diseases requiring treatment;
6. Live vaccines were administered within 30 days before administration of the study drug;
7. Active autoimmune diseases requiring systemic treatment in the past 12 months (i.e. the use of drugs to improve the disease, corticosteroids or immunosuppressive drugs). Note: alternative therapy (such as thyroxine, insulin or physiological corticosteroid replacement therapy with adrenal or pituitary insufficiency, etc.) is not considered as a systemic treatment;
8. Known allergy or severe reaction to IBI376 or rituximab or any excipients;
9. History of severe allergic reaction;
10. There is congestive heart failure or uncontrolled arrhythmia classified as III-IV by the New York Heart Association;
11. Patients with clinically significant electrocardiogram abnormalities and potential risk of malignant arrhythmia;
12. Clinically significant heart diseases, including unstable angina pectoris, acute myocardial infarction and or heart problems, occurred within 6 months before study administration;
13. A history of stroke or intracranial hemorrhage within 3 months before the date of administration of the study drug;
14. Major surgery or severe trauma occurred within 28 days before the start of treatment, or major side effects have not recovered;
15. Major uncontrolled medical conditions, including but not limited to kidney, liver, blood, gastrointestinal tract, endocrine, lung, nerve, brain or mental diseases;
16. There were other malignancies in the first 3 years of the disease, but did not include cured basal or squamous cell skin cancer, superficial bladder cancer, prostatic intraepithelial neoplasia and cervical carcinoma in situ.
17. Known mental or physical diseases will interfere with the cooperation with the test requirements, or disturb the test results or the interpretation of the test results, and in the opinion of the treatment researcher, will make the patient unfit to participate in the study;
18. There are situations where the researcher's judgment will interfere with the whole process of the study; there are significant risks to the subjects; or interfere with the interpretation of the study data;
19. Pregnant or lactating patients;
20. Inability to swallow and retain oral drugs, malabsorption syndrome, diseases significantly affecting gastrointestinal function, total gastrectomy or small bowel resection, ulcerative colitis, symptomatic inflammatory bowel disease, partial or complete intestinal obstruction;
21. Any prohibited drug, including potent cytochrome P450 3A4 (CYP3A4) inhibitor or inducer, was used or expected to be used during the study 14 days before the administration of the study drug or within 5 half lives, whichever is longer;
22. Unable to understand or unwilling to sign the informed consent form.