An Open-label, Single-arm Clinical Study to Evaluate the Safety and Preliminary Efficacy of OriV508 Injection in Treating Relapsed/Refractory Hematological Malignancies

Inclusion Criteria

• •1. Aged 18 - 75 years.
• •2. ECOG scores 0-1.
• •3. Expected survival time ≥ 12 weeks.
• •4. Have a record of confirmed multiple myeloma (MM) according to IMWG criteria, or a record of histologically confirmed aggressive B-cell non-Hodgkin lymphoma (B-NHL). According to the definition of the 2022 World Health Organization (WHO) classification, the pathological types of aggressive B-NHL include: diffuse large B-cell lymphoma, not otherwise specified; diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements; high-grade B-cell lymphoma, not otherwise specified; primary mediastinal B-cell lymphoma; mantle cell lymphoma; grade 3b follicular lymphoma; large B-cell lymphoma transformed from indolent B-NHL.
• •5. For MM subjects only: (1) Have received at least 2 lines of anti-tumor therapy, with each line of therapy undergoing at least one complete treatment cycle, and have experienced disease progression during or within 12 months after the last treatment; or be judged by the investigator as double-refractory to immunomodulators and proteasome inhibitors, and did not achieve a minimal response (MR) or better during the last treatment or experienced disease progression within 60 days after the end of treatment. (2) Have measurable lesions during the screening period, meeting any of the following criteria: (a) Serum M-protein ≥ 0.5 g/dL; (b) Urine M-protein≥ 200 mg/24h; (c) Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratio is abnormal; (d) Plasma cell percentage ≥30% detected by bone marrow aspirate/biopsy; (e) Presence of at least one extramedullary lesion with a maximum diameter ≥ 2 cm.
• •6. For aggressive B-NHL subjects only: (1) Have received at least 2 lines of anti-tumor therapy, and are refractory to the last line of therapy (at least 2 cycles) (best response is PD or SD) or have experienced disease progression after the end of treatment. Previous treatments must include standard treatment regimens with anti-CD20 monoclonal antibodies (except for subjects with CD20-negative tumors) and anthracyclines; (2) Have at least one measurable lesion during the screening period: lymph node lesions must have a longest diameter \> 1.5 cm, and extranodal lesions must have a longest diameter \> 1.0 cm.
• •7. Hemogram meets the following requirements:
• •* Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week prior to screening, recombinant human erythropoietin is permitted);
• •* Absolute neutrophil count (ANC) ≥ 750 /μL (no granulocyte colony-stimulating factor (G-CSF) used within 1 week prior to screening or no pegylated G-CSF used within 2 weeks prior to screening);
• •* Platelet count ≥ 50,000 /μL;
• •* Lymphocyte count ≥ 500 /μL.
• •8. Renal function: Creatinine clearance (CrCl) (Modification of Diet in Renal Disease (MDRD) formula) ≥ 40 mL/min/1.73m² (for MM subjects with CrCl \< 40 mL/min/1.73m², the investigator can decide whether to enroll based on clinical indications).
• •9. Liver function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert's syndrome or liver invasion by tumor, ALT and AST ≤ 5.0 × ULN and total bilirubin ≤ 3 × ULN are permitted).
• •10. Cardiac function: Left ventricular ejection fraction ≥ 45%.
• •11. Pulmonary function: Pulse oxygen saturation ≥ 92% without oxygen inhalation.
• •12. Women with childbearing potential must have a negative blood pregnancy test and not be in the lactation period.
• •13. Men and women with childbearing potential must agree to use effective contraceptive measures from the time of signing the informed consent form (ICF) until 1 year after the investigational drug administration.
• •14. Men and women with childbearing potential must agree not to donate reproductive cells such as sperm or eggs (oocytes) from the time of signing the ICF until 1 year after the investigational drug administration.
• •15. The participant or their legally authorized representative agrees to participate in this clinical trial and signs the ICF, indicating that he/she understands the objective and procedures of this clinical trial and is willing to participate in the study.