OH2 Injection in Combination With HX008 for Melanoma.

Inclusion Criteria:

1. The non-operative stage III or stage IV malignant tumor patients with clear diagnosis by pathology.
2. Patients who have failed in conventional treatment (including PD-1 monotherapy) (disease progression or intolerance) or who have failed in previously assisted PD-1 monotherapy (last assisted PD-1 treatment relapse or metastasis within 6 months).
3. Patients with Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1, expected survival time more than 3 months.
4. Prior anti-tumor treatment (including endocrine, chemical/ radiotherapy,targeted therapy) was over 4 weeks (more than 6 weeks of discontinuation using nitroso-and mitomycin-based chemotherapy) and was recovered to grade 1 from the side effects of prior treatment.
5. There is at least one measurable lesion that is suitable for intratumoral injection. The measured tumor focus is defined as the longest diameter ≥ 5 mm.
6. Asymptomatic central nervous system metastasis, or treated asymptomatic brain metastasis patients, must be examined by a computerized fault scan (CT) or MRI for disease-free progression, stable for at least 3 months, and at least 4 weeks without steroid medication.
7. (a) WBC≥3.0×109／L，ANC≥2.0×109／L ，PLT≥100×109／L，Hb≥90 g/L； (b) BUN and Scr. were in the upper limit of 1.5 times of the normal value; (c) TBIL≤ 1.5 times the upper limit of the normal value. (d) ALT and AST ≤ 2.5 times the upper limit of normal value; The value of patients with liver metastasis did not exceed 5 times the upper limit of normal value. (e) Coagulation function is normal (PT and APPT are within 1.5 times of the upper limit of normal value).
8. Female subjects and their spouses received effective contraceptives during and within 3 months of treatment.
9. Subjects with herpes in the reproductive organs needed three months after the end of herpes.
10. The informed consent was voluntarily signed and the expected compliance was good.

Exclusion Criteria:

1. Severe medical diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infection, active digestive tract ulcer, abnormal immune function (including, but not limited to, rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, etc.).
2. Significant surgery is expected to be performed during the 28-day screening period during the study period.
3. Patients had active infections or unexplained fevers (over 38.5℃)during screening and before the first drug use.
4. Past or present immunodeficiency diseases.
5. The lesions do not meet the requirements of injection capacity(1ml) in the tumor body.
6. Pregnant or lactating women.
7. Other experimental therapies or antiviral therapy are used or are being used within 4 weeks of treatment.
8. Allergy to herpes virus and drug ingredients.
9. History of primary grape-film melanoma or other malignant tumors in the 5 years prior to treatment.
10. History of tuberculosis, or have tuberculosis at the time of screening.
11. Suffering from sudden lung disease, intersex lung disease, intersex pneumonia, pulmonary fibrosis, acute lung disease, radioactive pneumonia etc.
12. Patients with active autoimmune diseases or with a history of autoimmune diseases that may relapse, except for:

    1. Type I diabetes with stable condition after taking a fixed dose of insulin;
    2. Hypothyroidism;
    3. Controlled celiac disease;
    4. Skin diseases that do not require systemic treatment;
    5. Any other disease that does not re-occur without external triggers.
13. Concurrent medical condition requiring the use of cortisol (\>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment, except for inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent.
14. The researchers believe that there is any reason why the patient is not suitable to participate in this trial.