A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )

Inclusion Criteria: 1. Patient with histologically proven stage IIIc or stage IV melanoma who fails to qualify for curative surgery and who bears one or more tumors that are accessible for direct injection 2. Patient must have had no more than one previous systemic regimen for management of melanoma; however, adjuvant chemotherapy administered 6 months or longer before entering the trial does not count as a line of treatment 3. Absence of circulating serum neutralizing antibodies to CVA21 (titer \< 1:16) 4. At least one tumor 0.5 to 10 cm in the longest diameter must be suitable for injection and at least one tumor must be equal to or greater than 1 cm and qualified to be a target lesion for RECIST 1.1 criteria 5. Patient must have adequate hematologic, hepatic and renal function, defined as: * Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L * Bilirubin \< 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) \< 2.5 x ULN * Serum creatinine \< 1.5 x ULN; if \> 1.5 x ULN, it must be confirmed that creatinine clearance \> 30 mL/minute 6. Serum lactate dehydrogenase (LDH) levels \< or = 1.5 x ULN 7. Male or female age 18 years or older 8. Performance status (Eastern Cooperative Oncology Group \[ECOG\]) 0 or 1 9. Estimated life expectancy of more than 6 months 10. Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy 11. Patient is able and willing to provide written informed consent to participate in the study 12. Fertile males and females must agree to the use of an adequate form of contraception, e.g., condoms for males. A negative pregnancy test is required in female patients of childbearing potential. Exclusion Criteria: 1. Mucosal or ocular primary tumors 2. Bone metastases 3. Greater than 3 visceral metastases 4. Any visceral metastases \> 10 cm 5. Serum anti-CVA21 neutralizing titer of \> 1:16 at baseline 6. Presence of any central nervous system (CNS) tumor that has not been stable for at least 3 months off corticosteroids and confirmed by imaging 7. Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion into a major vessel in the case of necrosis 8. Only measurable tumor had prior local radiotherapy without subsequent nodule progression 9. Patient has received chemotherapy within the last 4 weeks prior to first injection 10. ECOG score greater than 1 11. Estimated life expectancy of less than 6 months 12. Pregnancy or breastfeeding 13. Primary or secondary immunodeficiency, including immunosuppressive disease, and immunosuppressive doses of corticosteroids (e.g., prednisolone \> 7.5 mg per day) or other immunosuppressive medications including cyclosporine, azathioprine, interferons within the past 4 weeks prior to screening 14. Positive serology for human immunodeficiency virus (HIV), hepatitis B or C 15. Full dose anticoagulation or a history of bleeding diathesis or poorly controlled bleeding in the last month prior to screening 16. Previous splenectomy 17. Presence of uncontrolled infection 18. Presence of unstable neurological disease 19. Any uncontrolled medical condition that, in the opinion of the investigator, is likely to place the patient at unacceptable risk during the study or reduce his/her ability to complete the study 20. Participation in another study requiring administration of an investigational drug or biological agent within the last 4 weeks prior to screening 21. Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent 22. Participation in any previous melanoma immunotherapy trial within 1 month prior to entry to this trial or any trial of any other investigational agent within the last month prior to entry to this trial 23. Active infections or serious general medical conditions 24. Patients with previous malignancies should only be permitted if they have been in a continued state of "no evidence of disease" for at least 5 years with the exception of adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of the breast, and basal cell/squamous cell skin cancer 25. Known allergy to treatment medication or its excipients and/or to the contrast medium