Trial of an Intratumoral Injections of INXN-3001 in Subjects With Stage III or IV Melanoma

The purpose of this study is to test the safety of an investigational combination drug/immunotherapy for the treatment of Stage III/IV melanoma.

This study will examine the effects of an oral Activator Ligand administration to modulate the timing of gene expression of human IL-12 by adenovirus-transduced dendritic cells injected into tumors.

Eligibility Criteria:
Inclusion Criteria:

1. Males or females of all races ≥ 18 years of age and ≤ 75 years of age;
2. Unresectable Stage III C (in transit) or Stage IV melanoma (M1a, M1b, M1c with LDH ≤ 2x ULN), arising from primary cutaneous, mucosal, or subungual melanoma of any tumor thickness or from an unknown primary site;
3. A minimum of 2-3 accessible nonvisceral lesions (longest diameter ≤3 cm) or palpable tumor-involved lymph nodes (longest diameter ≤5 cm) for intratumoral injections (INXN-3001) and biopsies;
4. ECOG performance status of 0 or 1;
5. Patients without visible brain metastases as assessed by contrast-enhanced MRI scan within 6 weeks prior to receiving study treatment;
6. Adequate baseline hematological and organ function, assessed by laboratory values within 42 days (6 weeks) prior to study entry and prior to repeat treatment cycles with INXN-1001 as follows: hemoglobin ≥ 10 g/L, granulocytes \> 2500/mm3, lymphocytes \> 1000/ mm3, platelets \> 100,000/ mm3, serum creatinine \< 1.5 x ULN, AST, ALT, alkaline phosphatase \< 2.5 x ULN, LDH ≤ 2 x ULN, serum bilirubin \< 1.5 x ULN, absolute neutrophils \> 500/ mm3;
7. An expected survival of at least approximately 6 months in the opinion of the investigator (as assessed mainly by performance status);
8. Females must be post-menopausal or surgically sterile or practice effective contraception; Men who are not surgically sterile and whose partners are not post-menopausal or surgically sterile must practice effective contraception;
9. Normal coagulation parameters as measured by PT/PTT;
10. Signed, IRB-approved voluntary written informed consent.

Exclusion Criteria:

1. Active, acute viral, bacterial, or fungal infections requiring specific therapy;
2. HIV-infection due to concerns about ability to mount an effective immune response;
3. Active autoimmune disease requiring steroids (\>10 mg prednisolone or comparable) or other immunosuppressive therapy;
4. Patients with detectable brain metastases at the time of screening (or within 6 weeks prior to receiving study treatment), as assessed by contrast-enhanced MRI scans;
5. Patients with one or more lesion(s) \> 3cm (LD) or palpable, tumor-involved lymph node(s) \>5 cm (LD);
6. Patients with a hemoglobin of \< 10 g/L;
7. Presence of Stage IV visceral metastases or other distant metastases if LDH \>2 x ULN;
8. Patients who have previously been treated with INXN-3001 and INXN-1001;
9. Recipients of organ allografts;
10. Other concurrent, clinically active malignant disease, with the exception of other cancers of the skin;
11. Less than 30 days (before the first dose of study medication) have elapsed since the completion of prior chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any first line therapy;
12. Clinically significant cerebrovascular disease;
13. History of or concurrent severe cardiac insufficiency (New York Heart Association Class III or IV) or coronary artery disease;
14. QTc interval of \>470 ms on screening;
15. Inability to measure the QT interval due to conduction abnormalities such as Bundle Branch Block (left or right) or persistent cardiac arrhythmia e.g. atrial fibrillation, or cardiac pacemaker;
16. Long QT syndrome or family history of sudden cardiac death in young family members;
17. Concomitant use of medication known to affect ventricular repolarization;
18. Cardiac comorbidity such as a left ventricular ejection fraction \<45%, myocardial infarction, persistent angina, or cardiac surgery within 3 months prior to enrollment;
19. Uncontrollable hypertension (\>150 mm Hg systolic or \>100 mm Hg diastolic);
20. Acute medical conditions such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk;
21. History of or current bleeding or uncorrected clotting disorders;
22. Concurrent immunosuppressive therapy such as corticosteroids (\>10mg prednisolone or comparable) and cyclosporin A;
23. Concurrent investigational treatments, or treatment with any investigational treatment within the past 30 days (prior to the first dose of study medication);
24. Concurrent medications that are metabolized by the CYP 3A4 pathway;
25. Females who are lactating or pregnant;
26. A Body Mass Index (BMI) greater than or equal to 40 kg/m2; aa. Patients who have a history of hypersensitivity that may relate to any component of the product, e.g. to benzoic acid that might be related to INXN-1001, which contains two benzene rings; bb. Any medical or psychiatric condition which, in the opinion of the investigator, would unacceptably reduce the safety or delivery of the proposed treatment, or would preclude obtaining voluntary informed consent.