Intratumoral Injection of PV-001-DV Plus DC in Patients With Melanoma

Exclusion Criteria

• •1. Patients with positive antibody to any Dengue Virus serotype by tetravalent ELISA assay.
• •2. Patients with prior vaccinations or positive Ab detected by ELISA to: West Nile, St. Louis Encephalitis, or Yellow Fever
• •3. Pre-existing autoimmune or antibody mediated disease including systemic lupus erythematous, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
• •4. Known history of human immunodeficiency virus (HIV) or any active immunosuppressive systemic infection or a suppressed immune system, including acquired immuno-deficiency syndrome (AIDS) or HIV positivity and known hepatitis B or C infections (HCV or HBC), as assessed by serology.
• •5. Patients on immunosuppressive therapy. Concurrent steroid use of not more than an equivalent of 10 mg of prednisone is allowed.
• •6. Any other open wounds.
• •7. Previous organ transplantation.
• •8. Patients with clinically significant dermatological disorders, as judged by the clinical investigator (e.g., eczema or psoriasis), any skin lesions or ulcers, any history of atopic dermatitis, or any history of Darier's disease (Keratosis Follicularis).
• •9. Patients with White Blood Cell count \<1,500/uL; platelet count \<100,000/mm3; absolute neutrophil count (ANC) 1,500/mm3 (Grade 2)
• •10. Patients with inadequate renal function by serum creatinine of \>1.5 x ULN (Grade 2)
• •11. Patients with inadequate liver function by SGPT/SGOT \> 3x ULN, and bilirubin \>2.5 mg/dl (Grade 2)
• •12. Patients with active infection or with a fever \>101°F (38.5°C) within 3 days prior to the first scheduled treatment.
• •13. Concurrent participation in other treatment related clinical studies. Non-treatment studies (e.g. observation or tumor cell analysis studies) are allowed.
• •14. Prior malignancy (active within 3 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix.
• •15. Significant cardiovascular disease (i.e., New York Heart Association (NYHA) class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
• •16. Female patients who are pregnant or lactating.
• •17. Patients taken off Checkpoint Blockade agents: Ipilimumab, Nivolumab, Pembrolizumab, for Grade 3 or greater autoimmune toxicity. \[7\]
• •18. Patients who are positive for B-RafV600 mutation and are responding to targeted therapy.
• •19. Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with his/her participation in the study, or to interfere with the interpretation of the results.
• •20. Patients with endocrinopathy greater than grade III.
• •21. Patients who have undergone a splenectomy in their previous medical history will be excluded from this trial. Evidence of a splenectomy will be from history or records.
• •22. Prior history or serologic evidence of other flavivirus infections (yellow fever, St. Louis encephalitis, West Nile virus)
• •23. Prior history of having received a flavivirus vaccine
• •24. Patients who are actively taking Non Steroid Anti Inflammatory Drugs (NSAID) including aspirin