Safety Study of Adenovirus Vector Engineered to Express hIL-12 in Combination With Activator Ligand to Treat Melanoma

Single-arm, open label, Phase I/II dose escalation study of intratumoral injections INXN-2001 and oral INXN-1001 in subjects with unresectable Stage III or IV melanoma.

Four sequential dose escalation cohorts of INXN-1001 in combination with a fixed dose of INXN-2001 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design.

Approximately 15 additional subjects will be enrolled as an expansion cohort at a single dose level at or below the MTD.

• Safety and tolerability will be assessed by the incidence and severity of adverse events.
• The antitumor activity of study treatment will be assessed according to RECIST v1.1 guidelines. Additional assessment of anti-tumor activity will be explored based on total measurable tumor burden.
• Immunological and biological markers of response will include examinations of tumor biopsy samples, cytokine levels, peripheral blood mononuclear cells (PBMC) and antibody response to INXN-2001.

Inclusion criteria

• Males or females of all races ≥ 18 years of age, who have provided written informed consent prior to completing any study specific procedure.
• Unresectable Stage III or Stage IV melanoma arising from any site other than ocular melanoma.
• A minimum of 2 accessible nonvisceral lesions (shortest diameter ≥1 cm) or palpable tumor-involved lymph nodes (shortest diameter ≥1.5 cm).
• ECOG performance status of 0 or 1 (Appendix 1).
• Adequate bone marrow, liver, and renal function.
• An expected survival of at least approximately 6 months.
• Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug.

Exclusion criteria

• Any prior anti-cancer therapy or investigational agent within 28 days prior to the first dose of study drug. (NOTE: For the expansion cohort ONLY, if subjects received ipilimumab, a 90-day washout period since last dose of ipilimumab is required. If subjects received other immunomodulating therapies (eg, anti-PD1 antibodies), the medical monitor should be contacted and an evaluation will be made.)
• Clinically significant infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks of the first dose of study drug.
• History of HIV infection.
• Active autoimmune disease requiring steroids (>10 mg prednisone or comparable) or other immunosuppressive therapy (e.g., methotrexate, etc.).
• Documented symptomatic brain metastases. Screening for brain lesions by CT or MRI is not required for all potential subjects; however, if there are any neurological signs or symptoms consistent with brain metastases, then a brain CT or MRI should be performed as clinically indicated.
• Any medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first dose of study drug.
• Prior history of hematopoietic stem cell transplant or organ allograft.
• Other concurrent clinically active malignant disease, with the exception of other cancers of the skin.
• Females who are nursing or pregnant.
• Subjects who have a history of hypersensitivity that may relate to any component of the study drugs, e.g. to benzoic acid since INXN-1001 contains two benzene rings.
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.