Evaluate Efficacy, Immunological Response of Intratumoral/Intralesional Oncolytic Virus (OBP-301) in Metastatic Melanoma

Inclusion Criteria: 1. Histologically or cytologically confirmed malignant melanoma at Screening that is unresectable/unresected Stage IIIB, IIIC, IIID or IV. Patients with unresectable mucosal melanoma may be enrolled after consultation with the Medical Monitor. 2. Patients must have received and failed or refused available therapy for unresectable/unresected Stage III or IV melanoma. 3. Patients must be ≥ 18 years of age. 4. At least 2 cutaneous, subcutaneous and/or lymph node target lesions that are greater or equal to 1 cm in the longest diameter. One of the cutaneous, subcutaneous and/or lymph node target lesions should be designated at Screening as a noninjected target lesion. Willing to have biopsy specimens taken at Screening and at Week 6. 5. Life expectancy of ≥ 6 months from the first OBP-301 treatment. 6. Karnofsky Performance Status Scale (KPS) score of ≥ 70. 7. Adequate organ function, hematologic status, coagulation status, kidney function, and liver function as follows: * Absolute neutrophils \> 1,500/µL * Hemoglobin \> 9 g/dL, without transfusion or hematopoietic growth factor * Platelets \> 100,000/µL. Patients with ≤ 100,000 platelet count may be allowed into the study on a case-by-case basis after consultation with the Medical Monitor. * Serum creatinine \< 2 × upper limit of normal (ULN) * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2 × ULN except for patients with known liver metastases, in which case aspartate transaminase or alanine transaminase may be ≤ 5.0 × ULN * Total bilirubin \< 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's syndrome) * Serum lactate dehydrogenase (LDH) levels \< 1.5 × ULN 8. Understand the study requirements and the treatment procedures, and is willing to comply with all specified follow-up evaluations, and provides written informed consent before any study-specific tests or procedures are performed. 9. Patients of reproductive potential must use effective contraception for the duration of the study and for 3 months (90 days) after the last administered injection of OBP-301. Effective contraception includes oral contraceptives, implantable hormonal contraception, double-barrier method or intrauterine device. Exclusion Criteria: 1. Patients who have had administration of chemotherapy, target therapy, and/or immunotherapy within the last 4 weeks before the first OBP-301 administration. 2. Patients who have received other investigational medication within the last 4 weeks or a period of its 5 half-lives (whichever is shorter) before the first OBP-301 administration. 3. Patients who have had radiotherapy within the last 4 weeks before the first OBP-301 administration. 4. Effects of any other prior therapies not reverted to ≤ Grade 1 (or ≤ Grade 2 for alopecia and peripheral neuropathy). 5. Patients who have any liver metastases or visceral metastasis of ≥ 3 cm, plus evidence of progression meeting irRC 1.0 within 1 month before the first OBP-301 administration. 6. Patients with clinically active brain metastases. However, patients with previously currently stable brain metastases on medication (i.e., steroids and/or anti-seizure medications) may be enrolled after consultation with the Medical Monitor. 7. Patients known to have acute or chronic active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). 8. Patients diagnosed with additional malignancy within 3 years before the first OBP-301 administration with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers. 9. Patients requiring chronic systemic immunosuppressive medication including pharmacologic dose of glucocorticoids or cyclosporine should be evaluated by the Medical Monitor for enrollment eligibility. 10. Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/psychological incompetence, whereby in the opinion of the Investigator the patient is assessed as being unable to provide information, consent, or comply with the study requirements and procedures. 11. Patients who are pregnant or breastfeeding, or expecting to conceive or father children within the projected timeframe of the study, starting from the time of the Screening Visit through 3 months (90 days) after the last OBP-301 administration. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at each visit before administration of OPB-301. A female not of childbearing potential is one who has undergone bilateral oophorectomy or who has had no menses for 12 consecutive months.