OH2 Oncolytic Viral Therapy in Advanced Bladder Cancer

Inclusion Criteria:

1. Agree to sign informed consent, willing to follow the study procedures.

2. Age 18 ~ 75 years old (including boundary value), male or female.

3. ECOG 0-1.

4. Histologically or cytologically confirmed advanced bladder cancer，relapsed andmetastasized after radiotherapy or immunotherapy.

5. Life expectancy >12 weeks.

6. Agree to provide last surgical specimens (including paraffin blocks, paraffinembedded sections, etc.).

7. At least 6 weeks after previous anti-tumor treatment (radiotherapy, chemotherapy andimmunotherapy) and the first administration of this trial.

8. Appropriate organ function and hematopoietic function: neutrophil count (neut ≥ 1.5 × 109/L； White blood cell count (WBC) ≥ 3.0 × 109/L； Platelet count ≥ 100 × 109/L；Hemoglobin ≥ 90g / L; Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 2.5 times ULN; Serum total bilirubin ≤ 1.5 times ULN; Activatedpartial thromboplastin time (APTT) ≤ 1.5 times ULN (except for patients undergoinganticoagulant therapy).

9. Agree to take effective contraceptive measures during treatment and at least 180days after the last treatment.

Exclusion Criteria:

1. The primary tumor was upper urinary tract and ureteral urothelial carcinoma.

2. Malignant tumors other than bladder urothelial carcinoma within 5 years beforeenrollment. except:

①Prostate cancer with local low risk (stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20ng /ml, no recurrence after treatment (judged by reviewing PSA level)).

②Low risk prostate cancer (stage T1 / T2a, Gleason score ≤ 7, and PSA ≤ 10NG / ml,in the observed but untreated stage.

③For malignant tumors that meet other inclusion criteria but have a very low risk ofmetastasis or death, after standard treatment, recheck the patients whose imagingand disease-specific tumor markers show no recurrence or metastasis, such as fullytreated cervical cancer in situ, basal or squamous cell skin cancer; Ductalcarcinoma in situ after treatment and operation.

3. Active autoimmune diseases and need systemic treatment in the past two years (i.e.long-term use of corticosteroids or immunosuppressive drugs). Alternative therapies (such as thyroxine, insulin or physiological corticosteroid replacement therapy foradrenal or pituitary insufficiency) are excluded.

4. Expected to have major surgery during the study period or had major surgery within 4weeks before administration.

5. Received other vaccines within 30 days before the first administration (includingnew crown vaccine)

6. Any immune related toxicity caused by previous cancer treatment did not return to ≤grade 1 (except for grade 2 endocrine system diseases receiving stable dose hormonereplacement therapy), and / or any other toxicity related to previous anti-cancertreatment (except immune related toxicity) did not return to ≤ grade 2, except hairloss.

7. Human immunodeficiency virus (HIV) seropositive or history of HIV infection or otheracquired immunodeficiency diseases.

8. Long-term use of antiviral drugs, including hepatitis B (HBsAg positive and HBV DNAequal to 2000 IU/ml at the same time, and excluding hepatitis or other causes ofhepatitis), hepatitis C (at the same time to meet the anti HCV antibody positive,and HCV-RNA fruit is greater than the lower limit).

9. Uncontrolled systemic diseases, such as cardiovascular and cerebrovascular diseasesand diabetes.

10. History of organ transplantation or stem cell transplantation.

11. Cardiac insufficiency (patients classified as III-IV according to NY-HA of New YorkHeart Association).

12. Lung disease (such as shortness of breath during rest or slight activity or oxygensupplement for any reason).

13. Other basic diseases which would interfere with the diagnosis of the disease, ormight potentially cause serious complications

14. Other serious infections before administration

15. Alcohol addicts or history of drug abuse.

16. History of neurological or mental disorders, such as epilepsy, dementia, poorcompliance, or peripheral nervous system disorders.

17. Pregnancy or lactation, or expected pregnancy or childbirth during the trial period.

18. Allergic to study drug or have a history of allergic reaction to the main andauxiliary materials of any dosage form in the study drug.