PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

Inclusion Criteria: 1. Age 18 years or older, male or female 2. Histologically or cytologically confirmed melanoma 3. Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma metastases (i.e., American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases) 4. At least 1 measurable Target Lesion that can be accurately measured by calipers or computed tomography (CT) consisting of: * at least one cutaneous lesion (each lesion ≥ 10 mm in longest diameter or up to 5 lesions having a sum of longest diameters ≥ 10 mm); and/or * at least one subcutaneous lesion (each lesion ≥ 10 mm in longest diameter by CT); * where Target Lesions should be at least 10 mm from any other lesion 5. No lesion \> 50 mm in longest diameter; and no more than 50 lesions 6. Calculated required PV-10 dose ≤ 15 mL (based on total tumor burden) 7. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2 8. Not a candidate for treatment with an immune checkpoint inhibitor (e.g., failed or did not tolerate prior therapy, or due to co-morbidities, pre-existing autoimmune disease, drug unavailability or standard of care) 9. Not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (e.g., failed or did not tolerate prior therapy, BRAF V600 wild-type or due to drug unavailability or standard of care) 10. Clinical Laboratories: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L and platelet count ≥100 x 10\^9/L * Creatinine ≤ 3 times the upper limit of normal (ULN) * Estimated creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 * Total bilirubin ≤ 3 times the upper limit of normal (ULN) * Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) ≤ 5 times the upper limit of normal (ULN) * Lactate dehydrogenase (LDH) ≤ 2 times the upper limit of normal (ULN). 11. Thyroid function abnormality ≤ Grade 2 12. Candidate for at least one comparator drug: * Subjects must be candidates for at least one of the designated comparator drugs Exclusion Criteria: 1. Presence or history of visceral melanoma metastasis 2. Presence of active nodal metastases (e.g., radiologic or clinical evidence of current nodal disease) 3. Presence of more than 50 melanoma lesions 4. Radiation therapy to any Study Lesion within 6 weeks of initial study treatment. 5. Chemotherapy or other systemic cancer therapy within 4 weeks of initial study treatment (6 weeks for nitrosoureas or mitomycin), or regional chemotherapy (limb infusion or perfusion) within 12 weeks of initial study treatment 6. Immunotherapy for cancer within 4 weeks of initial study treatment 7. Local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion within 4 weeks of initial study treatment 8. Anti-tumor vaccine therapy within 6 weeks of initial study treatment. 9. Investigational agents within 4 weeks of initial study treatment. 10. Concurrent or Intercurrent Illness: * Impaired wound healing or other extremity complications due to diabetes mellitus in subjects whose Study Lesions are located in an extremity * Severe peripheral vascular disease in subjects whose Study Lesions are located in an extremity * Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise the subject's safety or compliance or interfere with interpretation of study results. * Uncontrolled thyroid disease or cystic fibrosis * Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders 11. Pregnancy: * Female subjects who are pregnant or lactating * Female subjects who have positive serum pregnancy test taken within 14 days of study treatment * Female subjects of child-bearing potential who are unwilling to use highly effective contraception (e.g., combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives, intrauterine devices, bilateral tubal ligation, vasectomized partner, sexual abstinence or equivalent measures) for the duration of study treatment 12. Contraindication for all comparators: * Subjects with contraindications to all of the designated comparator drugs