Safety and Efficacy of EX103 in Subjects with Relapsed/Refractory CD20-Positive Non-Hodgkin Lymphoma

Inclusion Criteria:

1. Provision of signed and dated informed consent form; stated willingness to complywith all study procedures and availability for the duration of the study; 2. Aged ≥ 18 years old, male or female; 3. Meeting the following criteria:

2. Dose-escalation phase: (1) with CD20-positive non-Hodgkin lymphoma confirmed at thefirst diagnosis (excluding patients whose CD20 turned negative after rituximabtreatment); (2) with relapsed or refractory disease after least 2 prior lines ofsystemic therapy; (3) currently with no suitable therapy available for prolongingsurvival;

3. Dose-expansion phase:

(i) Cohort 1:

1. Histopathologically and immunohistochemically confirmed CD20-positive diffuse largeB-cell lymphoma (DLBCL) (excluding patients whose CD20 turned negative afterrituximab treatment) : including non-specific (NOS) DLBCL, high-grade B-celllymphoma (HGBCL), primary mediastinal (thymus) large B-cell lymphoma (PMBCL), andtranslational follicular lymphoma (trFL) (patients who have converted fromfollicular lymphoma to DLBCL can be enrolled, and pathology reports should beprovided at the same time if there is a disease transformation), or follicularlymphoma (FL) with histological grade 3b; the sponsor may limit the number ofpatients 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 whichincluded anthracyclines);

(ii) Cohort 2:

1. Histopathologically and immunohistochemically confirmed CD20-positive follicularlymphoma (FL) (excluding patients whose CD20 turned negative after rituximabtreatment);

2. The histological grade ranged from 1 to 3a;

3. Previous failure or recurrence of second-line or higher systemic regimens (at leastone of which included anti-CD20 targeted therapies and alkylating agents; Thesponsor may limit the minimum number of patients who are refractory to bothanti-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-Hodgkinlymphoma (excluding patients with CD20 turning negative after rituximab treatment),other than the types included in cohort 1 and cohort 2; the sponsor may limit thenumber 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 leastone of which included a combination of anti-CD20 monoclonal antibodies andchemotherapy agents;

3. In cases of indolent lymphoma, indications for treatment must be present due tosymptoms and/or tumor burden;

4. At the dose escalation and expansion stages, the subjects must have at least onetwo- dimensionally measurable lesion as the basis for evaluation by CT, or MRI, ifCT is not applicable: for intranodal lesions, the long diameter is ≥ 1.5 cm; forextranodal 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 (bloodcomponents, short-acting cell growth factors, albumin, and other drugs are notallowed to be given within the first 7 days of laboratory tests; long-acting cellgrowth factors are not allowed to be given within the first 14 days):

8. Absolute neutrophil count ≥ 1.0×109/L;

9. Platelet count ≥ 50×109/L;

10. Hemoglobin ≥ 80 g/L;

11. Serum total bilirubin ≤ 1.5×ULN; if there is liver invasion, serum total bilirubin ≤ 3×ULN;

12. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; ifthere is liver invasion, ALT and AST ≤ 5×ULN;

13. Serum creatinine ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gaultformula ≥ 30 mL/min;

14. International normalized ratio (INR) or plasma prothrombin time (PT) ≤ 1.5×ULN;

15. Women of childbearing potential and men with a partner of childbearingpotential who consent to use highly effective methods of birth control duringtreatment and for an additional 90 days after the last administration of theprotocol specified treatment; women of childbearing age without surgicalsterilization must have a negative result in serum HCG test within 7 daysbefore enrollment in the study and isn't breastfeeding.

Exclusion Criteria:

1. Clear history of drug allergy, foreign protein, biologics or ingredients ofinvestigational drugs;

2. Uncontrolled active infection during the screening period;

3. Previously received allogeneic hematopoietic stem cell transplantation or solidorgan transplant; or received autologous hematopoietic stem celltransplantation (HSCT) or CAR-T cell therapy within 3 months;

4. CNS metastases, or other serious central nervous system diseases (such asepilepsy, cerebral infarction, and cerebral hemorrhage) within 6 months,History of neurodegenerative condition or CNS movement disorder. Subjects witha 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 evidencebelow are eligible for study entry:

6. Human immunodeficiency virus antibody (HIV-Ab) is negative;

7. Hepatitis B surface antigen (HBsAg) is negative; when HbsAg or HbcAb ispositive, HBV-DNA (HBV deoxyribonucleic acid) is < lower limit ofdetection;

8. Hepatitis C virus antibody is positive, and HCV RNA is negative.

9. 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 theinvestigator;

10. Develop any other malignancy within 5 years (except for completely treatedcervical carcinoma in situ or basal cell or squamous cell skin cancer);

11. Use of any vaccine within 4 weeks prior to initial pretreatment withdexamethasone or methylprednisolone or during the intended study period;

12. Systemic immunosuppressive drugs, including but not limited to radiotherapyimmune conjugate, antibody drug conjugations, immune/cytokines, monoclonalantibodies, etc., have been used within 4 weeks prior to initial pretreatmentwith dexamethasone or methylprednisolone.

13. With a history of active autoimmune diseases, including but not limited tomyocarditis, pneumonia, myasthenia gravis, autoimmune hepatitis, systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener'sgranulomatosis, multiple sclerosis, vasculitis, or glomerulonephritis;

14. Any condition that the investigator believes may not be appropriate forparticipating in the study.