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