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 arecord 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 largeB-cell lymphoma, not otherwise specified; diffuse large B-cell lymphoma/high-gradeB-cell lymphoma with MYC and BCL2 rearrangements; high-grade B-cell lymphoma, nototherwise 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, witheach line of therapy undergoing at least one complete treatment cycle, and haveexperienced disease progression during or within 12 months after the last treatment;or be judged by the investigator as double-refractory to immunomodulators andproteasome inhibitors, and did not achieve a minimal response (MR) or better duringthe last treatment or experienced disease progression within 60 days after the endof treatment. (2) Have measurable lesions during the screening period, meeting anyof the following criteria: (a) Serum M-protein ≥ 0.5 g/dL; (b) Urine M-protein≥ 200mg/24h; (c) Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratiois abnormal; (d) Plasma cell percentage ≥30% detected by bone marrowaspirate/biopsy; (e) Presence of at least one extramedullary lesion with a maximumdiameter ≥ 2 cm.

6. For aggressive B-NHL subjects only: (1) Have received at least 2 lines of anti-tumortherapy, and are refractory to the last line of therapy (at least 2 cycles) (bestresponse is PD or SD) or have experienced disease progression after the end oftreatment. Previous treatments must include standard treatment regimens withanti-CD20 monoclonal antibodies (except for subjects with CD20-negative tumors) andanthracyclines; (2) Have at least one measurable lesion during the screening period:lymph node lesions must have a longest diameter > 1.5 cm, and extranodal lesionsmust 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 toscreening, recombinant human erythropoietin is permitted);

• Absolute neutrophil count (ANC) ≥ 750 /μL (no granulocyte colony-stimulatingfactor (G-CSF) used within 1 week prior to screening or no pegylated G-CSF usedwithin 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 withGilbert's syndrome or liver invasion by tumor, ALT and AST ≤ 5.0 × ULN and totalbilirubin ≤ 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 notbe in the lactation period.

13. Men and women with childbearing potential must agree to use effective contraceptivemeasures from the time of signing the informed consent form (ICF) until 1 year afterthe investigational drug administration.

14. Men and women with childbearing potential must agree not to donate reproductivecells such as sperm or eggs (oocytes) from the time of signing the ICF until 1 yearafter the investigational drug administration.

15. The participant or their legally authorized representative agrees to participate inthis clinical trial and signs the ICF, indicating that he/she understands theobjective and procedures of this clinical trial and is willing to participate in thestudy.

Exclusion Criteria:

1. The subject has received the following therapy prior to signing the ICF:

• Small molecule targeted therapy, epigenetic therapy, or treatment with aninvestigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is longer;

• Immunosuppressive agent therapy (such as tacrolimus, mycophenolate mofetil,etc.) within 28 days;

• Monoclonal antibody treatment within 21 days;

• Cytotoxic therapy within 14 days;

• Proteasome inhibitor therapy within 14 days;

• Immunomodulator agent therapy within 7 days;

• Therapeutic dose of corticosteroids (defined as prednisone ≥ 20 mg/day orequivalent dose of other corticosteroids) within 72 hours, but physiologicalreplacement dose, topical and inhaled corticosteroids are permitted;

• Radiotherapy within 28 days (only for subjects whose radiation field covers > 5% of bone marrow reserve).

2. Received autologous hematopoietic stem cell transplantation within 24 weeks prior tosigning the ICF.

3. Received organ transplantation or allogeneic hematopoietic stem celltransplantation.

4. Have other malignant tumors prior to screening, except for the following cases:malignant tumors that have received radical treatment and have no known activedisease within 2 years prior to screening; or adequately treated non-melanoma skincancer with no evidence of active disease.

5. Previously treated with any viral therapy using vesicular stomatitis virus G (VSVG)-pseudotyped virus.

6. Known active central nervous system involvement or clinical signs of meningealinvolvement.

7. Complicated with severe uncontrolled active infections (bacterial, viral, fungal,etc.).

8. Have active autoimmune diseases (such as Crohn's disease, rheumatoid arthritis,systemic lupus erythematosus) or diseases requiring systemic application ofimmunosuppressive drugs.

9. Have hereditary bleeding/coagulation diseases, other diseases that may increase therisk of bleeding, etc.

10. Have active deep vein thrombosis (cancer emboli or thrombus) or pulmonary embolismwithin 12 weeks prior to signing the ICF, but if the investigator judges that thethrombus has been clinically treated and has no risk of detachment, enrollment ispermitted.

11. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA titer exceeding the normalrange; positive for hepatitis C virus (HCV) antibody with peripheral blood hepatitisC virus (HCV) RNA titer exceeding the normal range; positive for humanimmunodeficiency virus (HIV) antibody; positive for syphilis test.

12. Complicated with symptomatic heart failure or other severe cardiac diseases such asarrhythmia:

• New York Heart Association (NYHA) class III or IV congestive heart failure;

• Myocardial infarction, coronary artery bypass grafting (CABG) or coronary stentimplantation within 24 weeks prior to signing the ICF;

• Clinically significant ventricular arrhythmia, or history of unexplainedsyncope (except those caused by vasovagal or dehydration);

• Significant non-ischemic cardiomyopathy history.

13. Have other clinically significant diseases, including:

• Primary immunodeficiency;

• Stroke or epileptic seizure within 24 weeks prior to signing the ICF;

• Obvious clinical evidence of dementia or mental status changes;

• History of Parkinson's disease or Parkinson-like movement disorders.

14. Underwent surgery within 2 weeks prior to signing the ICF or plan to undergo surgerywithin 2 weeks after drug administration, except for surgery under local anesthesia.

15. Used attenuated/inactivated vaccines within 28 days prior to signing the ICF.

16. Known severe allergic reaction to OriV508 or its formulation components.

17. Known severe allergic reaction to tocilizumab.

18. Inability to establish venous access.

19. Other situations deemed unsuitable for participating in the study by theinvestigator.