Safety Study of Adenovirus Vector Engineered to Express hIL-12 (Human Interleukin 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.