This study is an open-label, Phase Ib clinical study to evaluate Evaluate the Recombinant Human GM-CSF Herpes Simplex Virus Injection (OrienX010) in Combination with Recombinant Human Anti-PD1 Monoclonal Antibody Injection (JS001) in the Treatment of Stage IV (M1c) Liver Metastasis from Melanoma.

This study is planned to enroll approximately 30 patients with Stage IV (M1c) Liver Metastasis from Melanoma who meet protocol requirements. This study is a single-arm clinical trial.

All participator will be given OrienX010 in combination with JS001. JS001 injection: 3 mg/kg, IV infusion: Once every 2 weeks ; OrienX010: Maximum injection volume 8 × 10^8 pfu, intratumoral injection: Once every 2 weeks. Treatment will be continuous and extend from first dose of study medication until to complete response, clinical related progression disease (PDr), intolerable AE, or withdrew informed consent or meet other criteria of discontinuation.

For patients who have stopped the study treatment and no disease progression, follow-up visits will take place every 3 months after the end of treatment visit until the occurrence of disease progression. If disease progression occurred, the investigator will collect the anticancer treatment information and survival of individuals until 80% death event.

Inclusion Criteria:

1. Obtain the current IRB approved informed consent with written from potential patients before the any screening activities or procedures.

2. Male or female, ≥ 18 years of age.

3. Patients with definite diagnosis of IV (M1c) Liver metastasis from melanoma based on histology and/or cytology.Patients who lack existing therapies or fail or relapse with existing therapies.

4. Patients with at least one injectable lesion on the liver (long diameter ≥ 10 mm and < 100 mm).

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

6. Expected Survival> 4 months;

7. The patients has good function in each organ, and the following conditions are required at screening according to the laboratory reference range:

   White blood cell count ≥ 3.0 × 109/L; Absolute neutrophil value ≥ 1.5 × 109/L; Platelet count ≥ 100 × 109/L; Hemoglobin ≥ 90 g/L; Serum albumin ≥ 2.5 g/dL; Liver function tests: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN; Renal function tests: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min at 24 hours (Cockcroft and Gault formula); International normalized ratio (INR) ≤ 1.5, and activated partial thromboplastin time (APTT) or partial prothrombin time (PTT) ≤ 1.5 × ULN;

8. Child-Pugh Grade A;

9. Patients receiving treatment for the first time in this study from the date of the last previous anti-tumor treatment date interval more than 28 days, and Patients have recovered from adverse events as a result of prior anti-tumor therapy to less than or equal to Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) (Except alopecia).

10. Female patients with childbearing potential (including premature menopause, menopausal < 2 years and non-surgical sterilization), male patients, and partners of male patients must agree to use effective contraception during the study: Surgical sterilization, oral contraceptives, intrauterine devices, sexual abstinence or barrier contraceptive combination spermicides; All patients must continue contraception for 6 months after the last treatment

Exclusion Criteria:

1. Patients previously treated with T-VEC or similar.
2. Patients previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2.
3. Patients with negative anti-herpes simplex virus type I (HSV-1) antibodies IgG and IgM.
4. The patient's lesion does not meet the requirement of the intratumoral injection volume or is not suitable for intratumoral injection.
5. Received anti-herpes simplex virus therapy (such as aciclovir, ganciclovir, valaciclovir, and arabinoside) within 4 weeks prior to the first dose of study treatment.
6. Received another anti-tumor monoclonal antibody (mAb) within 4 weeks prior to the first dose of study treatment or hasn't recover (≤ Grade 1) from adverse events due to prior therapy (occurring earlier than 4 weeks;
7. Patients with a history of other (including unknown primary) malignancies within 5 years prior to the first dose of trial treatment. Note: Except for fully treated stage 1 or 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or in situ cancer that is treated with potentially curative therapy.
8. Patients with known hypersensitivity to the study drug, its active ingredient, excipients.
9. Patient with HBsAg positive and HBV DNA copies > 1×10^3copies/mL.
10. Patients with positive hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies.
11. Patients with any unstable systemic disease, including but not limited to: Serious infection, uncontrolled diabetes mellitus, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardial infarction, congestive heart failure, and serious arrhythmia liver, kidney, or metabolic disease requiring medical treatment.
12. patients with active CNS metastases. patients may participate in the study if their CNS is adequately treated and their neurological symptoms recover to levels less than or equal to CTCAE1 for at least 2 weeks before enrollment, with the exception of residual signs or symptoms associated with CNS therapy . In addition, patients must be those who do not use corticosteroids or who take stable doses of ≤ 10 mg prednisone/day (or equivalent dose) or who decrease to ≤ 10 mg prednisone/day.
13. Patients with meningeal carcinomatosis.
14. Patients with autoimmune disease.
15. The disease (e.g., mental illness, etc.) or condition (e.g., alcoholism or drug abuse, etc.) of the patient may increase the patient's risk of receiving trial medication or affect the patient's compliance with the study requirements, or may confuse the study results.
16. Within 30 days of screening, the patient had received any other study product or had participated in another intervention clinical trial.
17. Pregnant or lactating women, or women who are prepared to become pregnant or lactating during the study; Men or women who are unwilling to use effective contraception.
18. Other situations that the investigators think are not suitable for inclusion.