pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Six male and/or female adult patients (greater than or equal to 18 years old), of any
ethnicity and race, with unresectable stage III or stage IV cutaneous melanoma with
accessible lesions, will be eligible for enrollment and treatment with IFx-Hu2.0.

To be eligible for this study, patients with unresectable metastatic disease must have
failed, refused or been deemed not candidates for at least one form of systemic
anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated. Talimogene
laherparepvec (IMLYGIC®) is indicated for local treatment of unresectable cutaneous,
subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.
Therefore, patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions
recurrent after initial surgery must have failed, refused or been deemed not candidates for
talimogene laherparepvec to be eligible for this study.

Enrollees will receive IFx-Hu2.0 at a single time point. Depending on the number of
accessible lesions, a patient could receive up to three doses across three lesions (one dose
per lesion). Forty milliliters of peripheral blood will be collected from these patients
prior to treatment administration and at the follow-up visit four weeks later. The target
dose will be 100 μg of plasmid DNA per lesion injected at a final dose volume of 200 μL per
lesion. To allow for the observation of any acute toxicity in the first subject enrolled and
prevent any occurrence of excessive toxicities in subsequent subjects, the first subject
enrolled will receive a single dose of IFx-Hu2.0. Subsequent subjects will be administered
the product after at least seven days. Beyond the first subject, the maximum number of
lesions to be injected at any given time point in the study phase proposed is three lesions.
These samples will be used to perform complete blood counts (CBC) and clinical chemistry
tests. A urine sample will be obtained for urinalysis for protein and blood at the same
frequency. Blood samples will be drawn for immune response evaluation as well. At the end of
the study period, a biopsy of the lesion injected and a non-injected lesion (if applicable)
will be collected. If the patient has a response to therapy, the patient will have the option
of continuing the study at three-week intervals so long as they have not progressed. Optional
tumor biopsies and peripheral blood collections may be obtained on subsequent treatment
cycles.

Inclusion Criteria:

- Histologically confirmed unresectable stage III or stage IV malignant melanoma, with
accessible cutaneous lesions

- Must have measurable disease greater than 3 mm

- At least one injectable lesion and one lesion for biopsy at study conclusion.
Lymphocyte count ≥ 500,000 cells/mL

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Willing and able to give written, informed consent

- If male or female of childbearing potential must be willing to use a contraceptive
during the study and for six months afterward. A woman is considered to be of
childbearing potential unless she has had a surgical procedure that would accomplish
sterility such a bilateral tubal ligation, hysterectomy or has not had menses for the
past 12 months.

- Life expectancy greater than three months

- To be eligible for this study, patients with unresectable metastatic disease must have
failed, refused or been deemed not candidates for at least one form of systemic
anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated.

- Patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions
recurrent after initial surgery must have failed, refused or been deemed not
candidates for talimogene laherparepvec to be eligible for this study.

- The entry laboratory criteria for subject eligibility must be less than or equal to
grade 1 adverse event levels for the parameters tested as defined by CTCAE v5.0.

Exclusion Criteria:

- Known brain metastases greater than 1 cm at screening.

- Life expectancy of fewer than three months

- Prior systemic anti-cancer treatment within three weeks from start of treatment (Day
0)

- Current treatment with systemic immunosuppressive corticosteroid (greater than 10 mg
of daily prednisone) doses or other immunosuppressants such as those needed for solid
organ transplants. Medications needed to treat conditions such as reactive airway
disease are not excluded.

- Pregnant or lactating women

- Presence of any uncontrolled and significant medical or psychiatric condition which
would interfere with trial safety assessments

- Treatment with any investigational product within the three weeks preceding injection

- Immunizations for encapsulated bacteria were not given for patients who have undergone
a splenectomy.

- Serious underlying medical or psychiatric conditions, active infections requiring the
use of antimicrobial drugs, or active bleeding that would make the subject unsuitable
or unable to participate in the study

- Concurrent chemotherapy or biological therapy. Concurrent radiotherapy is allowed as
long as it is not the same site as the injected lesion.

- Uncontrolled hepatitis B, hepatitis C, or HIV infection

- History of organ allograft transplantation