Inclusion Criteria:
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1\. Provision of signed and dated informed consent form; stated willingness to comply with all study procedures and availability for the duration of the study; 2. Aged ≥ 18 years old, male or female; 3. Meeting the following criteria:
1. Dose-escalation phase: (1) with CD20-positive non-Hodgkin lymphoma confirmed at the first diagnosis (excluding patients whose CD20 turned negative after rituximab treatment); (2) with relapsed or refractory disease after least 2 prior lines of systemic therapy; (3) currently with no suitable therapy available for prolonging survival;
2. Dose-expansion phase:
(i) Cohort 1:
1. Histopathologically and immunohistochemically confirmed CD20-positive diffuse large B-cell lymphoma (DLBCL) (excluding patients whose CD20 turned negative after rituximab treatment) : including non-specific (NOS) DLBCL, high-grade B-cell lymphoma (HGBCL), primary mediastinal (thymus) large B-cell lymphoma (PMBCL), and translational follicular lymphoma (trFL) (patients who have converted from follicular lymphoma to DLBCL can be enrolled, and pathology reports should be provided at the same time if there is a disease transformation), or follicular lymphoma (FL) with histological grade 3b; the sponsor may limit the number of patients with PMBCL and trFL enrolled;
2. Previous failure or relapse after second-line or higher systemic treatment regimens (at least one of which included anti-CD20 targeted therapy and at least one of which included anthracyclines);
(ii) Cohort 2:
1. Histopathologically and immunohistochemically confirmed CD20-positive follicular lymphoma (FL) (excluding patients whose CD20 turned negative after rituximab treatment);
2. The histological grade ranged from 1 to 3a;
3. Previous failure or recurrence of second-line or higher systemic regimens (at least one of which included anti-CD20 targeted therapies and alkylating agents; The sponsor may limit the minimum number of patients who are refractory to both anti-CD20-targeted therapies and alkylating agents);
4. Must be indicative of treatment due to symptoms and/or tumor burden;
(iii) Cohort 3:
1. Histopathologically and immunohistochemically confirmed CD20-positive non-Hodgkin lymphoma (excluding patients with CD20 turning negative after rituximab treatment), other than the types included in cohort 1 and cohort 2; the sponsor may limit the number of patients with certain or several specific tumor species to be enrolled;
2. Previous failure or relapse after second-line or higher standard treatment, at least one of which included a combination of anti-CD20 monoclonal antibodies and chemotherapy agents;
3. In cases of indolent lymphoma, indications for treatment must be present due to symptoms and/or tumor burden;
4\. At the dose escalation and expansion stages, the subjects must have at least one two- dimensionally measurable lesion as the basis for evaluation by CT, or MRI, if CT is not applicable: for intranodal lesions, the long diameter is ≥ 1.5 cm; for extranodal lesions, the long diameter is ≥ 1.0 cm;
5\. ECOG performance status score: 0-2;
6\. Life expectancy ≥ 12 weeks;
7\. The laboratory test results should be met before each cycle beyond cycle 1 (blood components, short-acting cell growth factors, albumin, and other drugs are not allowed to be given within the first 7 days of laboratory tests; long-acting cell growth factors are not allowed to be given within the first 14 days):
1. Absolute neutrophil count ≥ 1.0×109/L;
2. Platelet count ≥ 50×109/L;
3. Hemoglobin ≥ 80 g/L;
4. Serum total bilirubin ≤ 1.5×ULN; if there is liver invasion, serum total bilirubin ≤ 3×ULN;
5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver invasion, ALT and AST ≤ 5×ULN;
6. Serum creatinine ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gault formula ≥ 30 mL/min;
7. International normalized ratio (INR) or plasma prothrombin time (PT) ≤ 1.5×ULN;
8\. Women of childbearing potential and men with a partner of childbearing potential who consent to use highly effective methods of birth control during treatment and for an additional 90 days after the last administration of the protocol specified treatment; women of childbearing age without surgical sterilization must have a negative result in serum HCG test within 7 days before enrollment in the study and isn't breastfeeding.
Exclusion Criteria:
1. Clear history of drug allergy, foreign protein, biologics or ingredients of investigational drugs;
2. Uncontrolled active infection during the screening period;
3. Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplant; or received autologous hematopoietic stem cell transplantation (HSCT) or CAR-T cell therapy within 3 months;
4. CNS metastases, or other serious central nervous system diseases (such as epilepsy, cerebral infarction, and cerebral hemorrhage) within 6 months, History of neurodegenerative condition or CNS movement disorder. Subjects with a history seizure within 12 months prior to study enrollment are excluded;
5. At least one active person is known to have human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Subjects with evidence below are eligible for study entry:
1. Human immunodeficiency virus antibody (HIV-Ab) is negative;
2. Hepatitis B surface antigen (HBsAg) is negative; when HbsAg or HbcAb is positive, HBV-DNA (HBV deoxyribonucleic acid) is \< lower limit of detection;
3. Hepatitis C virus antibody is positive, and HCV RNA is negative.
6. Toxicities caused by previous anti-tumor therapy has not recovered to grade ≤ 1 (CTCAE v5.0), except alopecia and other tolerable events as determined by the investigator;
7. Develop any other malignancy within 5 years (except for completely treated cervical carcinoma in situ or basal cell or squamous cell skin cancer);
8. Use of any vaccine within 4 weeks prior to initial pretreatment with dexamethasone or methylprednisolone or during the intended study period;
9. Systemic immunosuppressive drugs, including but not limited to radiotherapy immune conjugate, antibody drug conjugations, immune/cytokines, monoclonal antibodies, etc., have been used within 4 weeks prior to initial pretreatment with dexamethasone or methylprednisolone.
10. With a history of active autoimmune diseases, including but not limited to myocarditis, pneumonia, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, multiple sclerosis, vasculitis, or glomerulonephritis;
11. Any condition that the investigator believes may not be appropriate for participating in the study.
