Study of Oncolytic Virus in Combination With HX-008 and Axitinib in Melanoma Patients With Liver Metastasis

Inclusion Criteria: 1. Voluntarily sign Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures; 2. Male and female, 18-75 years old (including boundary value); 3. Histologically confirmed stage IV melanoma with liver metastasis who lacks or becomes refractory to standard treatment; 4. Eastern Cooperative Oncology Group (ECOG) Performance Status is 0 or 1; 5. Expected survival at least 3 months; 6. The interval between the first administration and previous treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy and biotherapy for melanoma) in the past is over 4 weeks, and has recovered to grade 1 from the adverse reactions of previous treatment; 7. At least one measurable or evaluable lesion; 8. Liver metastasis has lesions suitable for intratumoral injection; 9. Asymptomatic central nervous system metastasis or asymptomatic brain metastasis after treatment must be confirmed by CT / MRI that there is no disease progression, stable for at least 3 months, and no steroid treatment for at least 4 weeks; 10. Appropriate organs and hematopoietic function according to the following laboratory tests: neutrophil absolute count (neut#) ≥ 2.0 × 109/L； Absolute white blood cell count (WBC) ≥ 3.0 × 109/L； Platelet ≥ 100 × 109/L； Hemoglobin ≥ 90g / L; Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 5 times ULN; Serum total bilirubin (TBIL) ≤ 1.5 times ULN; International normalized ratio (INR) ≤ 1.5 times ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (except for patients undergoing anticoagulant therapy); 11. Male patients and female subjects of childbearing age should agree to take effective contraceptive measures from the signing of informed consent to 3 months after the last administration; 12. Patients with herpes need 3 months after the end of herpes treatment. Exclusion Criteria: 1. Patients with a history of primary uveal melanoma or any other (including unknown primary) malignancy within 5 years before the first administration of the trial treatment. Note: 1 or 2 stage skin basal / squamous cell carcinoma, superficial bladder cancer or orthotopic carcinoma receiving potentially curative treatment are the most effective treatments; 2. Liver lesions are not suitable for intratumoral injection or do not meet the injection volume requirements; 3. Patients who had received anti herpes simplex virus treatment within 4 weeks before the first administration of the trial treatment, such as acyclovir, ganciclovir, valacyclovir, arabine adenosine, etc; 4. Patients with active or history of autoimmune diseases that may recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (such as organ transplantation and immunosuppressive treatment). However, subjects with the following diseases are allowed to be included in the group: * stable type 1 diabetic patients after a fixed dose of insulin. * autoimmune hypothyroidism or Hashimoto's thyroid inflammation requiring only hormone replacement therapy; * skin diseases that do not require systemic treatment (such as eczema, skin rash accounting for less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.); * celiac disease that has been controlled; * any other disease that will not recur without external inducing factors; 5. Patients with major surgery are expected to include a 28 day screening period during the study period; 6. Patients requiring systemic corticosteroids (equivalent to \> 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. However, you are allowed to join the group under the following conditions: * subjects were allowed to use topical or inhaled glucocorticoids; * allow short-term (≤ 7 days) use of glucocorticoids to prevent or treat non autoimmune allergic diseases; 7. Patients with active gastrointestinal ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding and perforation; 8. Patients suffering from interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease, acute radiation pneumonia, etc; 9. Uncontrolled stable systemic diseases such as cardiovascular and cerebrovascular diseases, hypertension, diabetes, tuberculosis and so on. 10. History of infection with human immunodeficiency virus, or suffer from other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation or stem cell transplantation; 11. patients with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA copy number \>1x103 copy /mL; 12. Patients with hepatitis C virus (HCV) antibody positive or human immunodeficiency virus (HIV) antibody positive; 13. Patients with severe infection within 4 weeks before the first administration, or patients with active infection requiring intravenous antibiotic treatment within 2 weeks before the first administration, and patients with unexplained fever \> 38.5 ℃ before the first administration; 14. Patients known to have severe allergic reactions to herpes virus, macromolecular protein preparation / monoclonal antibody, or any known test drug components (CTCAE v5.0 grade is greater than grade 3); 15. Participated in clinical trials of other drugs within 4 weeks before the first administration; 16. Alcohol addicts or have a history of drug abuse or drug abuse in recent 1 year; 17. Having a clear history of neurological or mental disorders, such as epilepsy, dementia, poor compliance, or peripheral nervous system disorders; 18. Pregnant or lactating women; 19. Patients who received live attenuated vaccine within 30 days before the first administration; 20. The researchers believe that patients who are not suitable to participate in the trial for other reasons.