IASO208 Injection in the Treatment of Relapsed/Refractory B-cell Malignancies

Inclusion Criteria Subjects must meet all of the following criteria to be enrolled in this study: 1. Aged ≥18 years and ≤75 years. 2. Voluntary participation in this study and signing the informed consent form. 3. Prior histopathological biopsy confirming a diagnosis of one of the following pathological types: * Diffuse Large B-Cell Lymphoma (DLBCL), including High-Grade B-Cell Lymphoma (HGBL); * Grade 3b Follicular Lymphoma (FL3b); * DLBCL transformed from indolent lymphoma (FL or MZL); * Primary Mediastinal Large B-Cell Lymphoma (PMBCL) and Mantle cell lymphoma. 4. For B-cell lymphoma patients with relapsed/refractory diseases who have failed standard treatment assessed by investigator (including relapse, non-remission, and progression); * Relapsed disease is defined as disease relapse or progression occurring ≥12 months after the end of prior therapy. * Refractory disease is defined as disease progression during treatment, best response of stable disease (SD), relapse within 12 months after autologous hematopoietic stem cell transplantation, or disease progression occurring within 12 months after the end of prior therapy. 5. CD20 positivity confirmed by detection on tumor biopsy specimens obtained after the last relapse or during the screening period. 6. Presence of at least one measurable lesion according to the Lugano 2014 criteria (nodal lesion with Long Axis Diameter \[LDi\] \>1.5 cm, extranodal lesion with LDi \>1.0 cm). 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 8. Life expectancy ≥12 weeks. 9. Adequate organ function, as demonstrated by the following laboratory results 1. Hematology: Absolute Neutrophil Count (ANC) ≥1.0 × 10⁹/L; Absolute Lymphocyte Count (ALC) ≥0.3 × 10⁹/L; Platelet count (PLT) ≥50 × 10⁹/L; Hemoglobin (Hb) ≥70 g/L (must not have received any Granulocyte Colony-Stimulating Factor \[G-CSF\] or Granulocyte-Macrophage Colony-Stimulating Factor \[GM-CSF\] treatment, or transfusion of red blood cells or platelets within 7 days prior to the laboratory assessment). 2. Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × Upper Limit of Normal (ULN); Total Bilirubin ≤ 2 × ULN (for subjects with documented liver involvement by tumor: ALT/AST ≤5 × ULN; Total Bilirubin ≤3 × ULN). 3. Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50%, as measured by echocardiography or Multigated Acquisition (MUGA) scan. 4. Oxygen saturation \>92% (by pulse oximetry) at rest. 5. Renal function: Creatinine Clearance (CrCl) ≥40 mL/min, calculated using the Cockcroft-Gault formula. 6. Coagulation profile: Fibrinogen ≥1.0 g/L; Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN; Prothrombin Time (PT) ≤1.5 × ULN. 10. Subjects of childbearing potential must agree to use highly effective contraceptive methods from the time of signing the informed consent form until at least 1 year after the last dose of IASO208 injection. Exclusion Criteria Subjects who meet any of the following criteria will be excluded from this study: 1. Subjects with central nervous system involvement. 2. Subjects who have had other malignancies within 5 years prior to screening, except for appropriately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma. 3. Subjects who meet any of the following conditions in infectious disease screening: 1. Subjects positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with abnormal peripheral blood HBV DNA test (abnormal HBV DNA is defined as: quantitative detection higher than the lower limit of detection \[LLD\], above the normal range, or positive qualitative detection). 2. Subjects positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA. 3. Subjects positive for human immunodeficiency virus (HIV) antibody. 4. Subjects with syphilis. 5. Subjects with active cytomegalovirus (CMV) infection. 4. Uncontrolled active bacterial, fungal, or viral infection prior to enrollment, as evidenced by: 1. Persistent infection-related symptoms/signs requiring intravenous anti-infective therapy; or 2. No improvement in clinical symptoms or examinations after appropriate anti-infective therapy. 5. Severe cardiac diseases, including but not limited to: unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association \[NYHA\] Class ≥ III), or severe arrhythmia. 6. History of central nervous system diseases or disorders within 6 months prior to screening, such as epilepsy, paralysis, aphasia, cerebral infarction, cerebral hemorrhage, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome (e.g., cerebral aneurysm, epilepsy, stroke \[except for lacunar infarction\], dementia, psychosis), or subjects with impaired consciousness. 7. Previous solid organ transplantation. 8. Previous allogeneic hematopoietic stem cell transplantation (allo-HSCT), allogeneic CAR-T therapy, or other allogeneic donor adoptive cell therapies. 9. Subjects who do not meet the required washout periods for the following prior therapies/treatments before enrollment: 1. Cytotoxic chemotherapy, monoclonal antibodies, bispecific antibodies, or antibody-drug conjugates (ADCs) within 4 weeks prior to enrollment. 2. Ongoing requirement for systemic corticosteroids or other immunosuppressive therapy within 4 weeks prior to enrollment. 3. Radiotherapy or major surgery of Grade 4 severity within 4 weeks prior to enrollment; or planned general anesthesia surgery within 12 weeks after receiving the study treatment. 4. Vaccination or treatment with any investigational products within 4 weeks prior to enrollment. 5. Autologous hematopoietic stem cell transplantation or autologous CAR-T therapy within 12 weeks prior to enrollment. 10. Presence of other unstable systemic diseases, as determined by the investigator, including but not limited to severe hepatic, renal, or metabolic diseases requiring treatment. 11. Adverse events from previous anti-tumor therapies have not resolved to baseline or Grade ≤ 2 (excluding alopecia, fatigue, and peripheral neuropathy). 12. Known history of hypersensitivity to any excipient component of the IASO208 injection. 13. Pregnant or lactating women. 14. Any other condition deemed by the investigator as inappropriate for participation in the study.