Safety Study of a Helper Peptide Vaccine Plus Adjuvant Combinations for the Treatment of Melanoma

Inclusion Criteria:

- Part 1 only: Participants with stage IIB, IIC, III, or IV melanoma at original
diagnosis or at restaging after recurrence. Patients with high-risk stage IIA melanoma
(by DecisionDx Melanoma test, Castle Biosciences, Inc,;Friendswood, TX) also may be
eligible. These participants may have had cutaneous, uveal, mucosal primary melanoma,
or an unknown primary melanoma. Diagnosis of melanoma must be confirmed by cytological
or histological examination. Staging of cutaneous melanoma will be based on version 7
AJCC staging system.

- Part 2 only: Patients with a diagnosis of stage IIIB-IV melanoma with one or more
tumor deposits accessible for biopsy and/or excision. These participants may have had
cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Diagnosis
of melanoma must be confirmed by cytological or histological examination. Staging of
cutaneous melanoma will be based on version 7 AJCC staging system.

Patients must have adequate cutaneous, subcutaneous, soft tissue, or nodal metastases of
melanoma readily accessible for biopsy

- Participants will be required to have radiological studies to rule out radiologically
evident disease. Required studies include:

- Chest CT scan,

- Abdominal and pelvic CT scan, and

- Head CT scan or MRI

- PET/CT fusion scan may replace scans of the chest, abdomen, and pelvis.

- Participants who have had brain metastases will be eligible if all of the following
are true:

- Each brain metastasis must have been completely removed by surgery or each
unresected brain metastasis must have been treated with stereotactic
radiosurgery.

- There has been no evident growth of any brain metastasis since the most recent
treatment.

- No brain metastasis is > 2 cm in diameter at the time of registration.

- The most recent surgical resections or gamma-knife therapy for malignant melanoma
must have been completed ≥ 1 week and for Part 1, ≤ 6 months prior to
registration.

- All participants must have:

- ECOG performance status of 0 or 1 (Appendix 3)

- Ability and willingness to give informed consent

- Laboratory parameters as follows:

- ANC > 1000/mm3

- Platelets > 100,000/mm3

- Hgb > 9 g/dL

- HgbA1c ≤ 7.5%

- Hepatic:

- AST and ALT ≤ 2.5 x upper limits of normal (ULN)

- Bilirubin ≤ 2.5 x ULN (except in patients with Gilbert's disease, where bilirubin
to 4x ULN is allowed)

- Alkaline phosphatase ≤ 2.5 x ULN

- Renal

- Creatinine ≤ 1.5 x ULN

- Serology (within 6 months of study entry)

- HIV negative

- Hepatitis C negative (no evidence of active virus)

- Blood is to be collected for HLA typing (Class I and Class II), which will be analyzed
as part of the immunologic endpoints, but HLA type will not be an inclusion/exclusion
criterion.

- Age 18 years or older at registration.

- Part 1 only: Participants must have at least two intact (undissected) axillary and/or
inguinal lymph node basins.

- Part 2 only: Participants must have at least one intact (undissected) axillary and/or
inguinal lymph node basin.

Exclusion Criteria:

- Participants who have received the following medications or treatments at any time
within 4 weeks of registration:

- Chemotherapy

- Interferon (e.g. Intron-A®)

- Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥
1 week and ≤ 6 months prior to registration)

- Allergy desensitization injections

- High doses of systemic corticosteroids, with the following qualifications and
exceptions:

- In patients with adrenal or pituitary insufficiency replacement steroid
doses are allowed; however, daily doses of 10 mg or more of prednisone (or
equivalent) per day administered parenterally or orally are not allowed in
patients with normal adrenal and pituitary function.

- Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low
doses (less than 500 mcg fluticasone per day, or equivalent) (76,77).

- Topical, nasal, and intra-articular corticosteroids are acceptable.

- Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)

- Interleukins (e.g. Proleukin®)

- Any investigational medication

- Targeted therapies specific for mutated BRAF or for MEK

- Participants who are currently receiving nitrosoureas or who have received this
therapy within the preceding 6 weeks

- Participants who are currently receiving a checkpoint molecule blockade therapy, or
who have received this therapy within the preceding 12 weeks.

- Participants with known or suspected allergies to any component of the vaccine.

- Participants may not have been vaccinated previously with any of the synthetic
peptides included in this protocol. Participants who have received vaccinations
containing agents other than the synthetic peptides included in this protocol and have
recurred during or after administration of the vaccine will be eligible to enroll 12
weeks following their last vaccination.

- Pregnancy. Female participants of childbearing potential must have a negative
pregnancy test (urinary or serum beta-HCG) obtained within 2 weeks prior to
registration. Males and females must agree, in the consent form, to use effective
birth control methods during the course of vaccination.

- Female participants must not be breastfeeding

- Participants in whom there is a medical contraindication or potential problem in
complying with the requirements of the protocol in the opinion of the investigator.

- Participants classified according to the New York Heart Association classification as
having Class III or IV heart disease (Appendix 4).

- Participants with uncontrolled diabetes, defined as having a HgbA1c ≥ 7.5%.

- Participants must not have had prior autoimmune disorders requiring cytotoxic or
immunosuppressive therapy, or autoimmune disorders with visceral involvement.
Participants with an active autoimmune disorder requiring these therapies are also
excluded. The following will not be exclusionary:

- The presence of laboratory evidence of autoimmune disease (e.g. positive ANA
titer) without symptoms

- Clinical evidence of vitiligo

- Other forms of depigmenting illness

- Mild arthritis requiring NSAID medications

- Participants who have another cancer diagnosis, except that the following diagnoses
will be allowed:

- squamous cell cancer of the skin without known metastasis

- basal cell cancer of the skin without known metastasis

- carcinoma in situ of the breast (DCIS or LCIS)

- carcinoma in situ of the cervix

- any cancer without distant metastasis that has been treated successfully, without
evidence of recurrence or metastasis for over 5 years

- Participants with known addiction to alcohol or drugs who are actively taking those
agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.

- Body weight < 110 pounds (without clothes) at registration, due to the amount and
frequency with which blood will be drawn.