Dendritic Cell Vaccination in Patients With Advanced Melanoma

This is a single arm open label trial that will assess the safety and tolerability of mature
dendritic cell (mDC3/8) vaccine (primer and booster) in subjects with stage III and stage IV
melanoma, followed by treatment with pembrolizumab (anti-PD-1 therapy).

Eligible patients that provide written informed consent will undergo apheresis to collect
blood mononuclear cells for vaccine production approximately 1 week prior to vaccine
infusion. Each study subject will receive cyclophosphamide 300mg/m^2 intravenously or by
mouth 3 to 4 days prior to the vaccine dose, to deplete regulatory T cells. For each vaccine
dose, all subjects will receive autologous dendritic cells pulsed with melanoma
tumor-specific peptides. On Day 1, the subject will receive the primer vaccine dose; this
will be followed by two booster vaccine doses at 6 weeks apart. Peripheral blood will be
taken weekly to monitor the immune response to each peptide by tetramer assay. Re-staging
will occur after the 3rd vaccine dose, along with tumor biopsy and second apheresis. Anti
PD-1 therapy (standard of care) will commence 7-8 weeks after the subject's last dendritic
cell vaccine.

Inclusion Criteria:

- Histologically confirmed stage III and stage IV M1a/M1b/M1c melanoma. Measurable
disease is not required for enrollment eligibility and patients with completely
resected disease are permitted.

- Male or female patients age greater than or equal to 18 years

- ECOG (Eastern Cooperative Oncology Group) performance status 0-2

- Required initial laboratory values (performed within 14 days prior to eligibility
confirmation by physician-investigator):

- WBC (white blood cells) >3,000/mm3

- Hg (hemoglobin) greater than or equal to 9.0 gm/dl

- Platelets >75,000/mm3

- Serum Bilirubin < 2.0 mg/dl

- Serum Creatinine < 2.0 mg/dl

- Subjects of reproductive potential must agree to use a medically accepted birth
control method during the trial and for at least two months following the trial.

- Provide written informed consent.

Exclusion Criteria:

- Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment
with one line of cytotoxic chemotherapy is permitted. Prior treatment with targeted
therapy (such as ipilimumab, anti-PD1, or BRAF + MEK inhibitor combination) is
permitted.

- Active untreated CNS (central nervous system) metastasis

- Active infection

- Prior malignancy (except non-melanoma skin cancer) within 3 years

- Pregnant or nursing (lactating) women

- Concurrent treatment with high-dose systemic corticosteroids; local (inhaled or
topical) steroids are permitted

- Known allergy to eggs

- Prior history of uveitis or autoimmune inflammatory eye disease

- Known positivity for hepatitis B antibody, hepatitis C antibody, or HIV antibody