Cohort 1 (Advanced): Measurable stage IIIB, IIIC, IIID or IV melanoma with clinical or
radiological evidence of disease. These participants may have had cutaneous, uveal, mucosal
primary melanoma, or an unknown primary melanoma. Staging must be confirmed by cytological
or histological examination. Staging of cutaneous melanoma will be based on the revised
AJCC 8th Edition staging system (Appendix 2) 66.
Cohort 2 (Neo-adjuvant): Resectable stage IIIB, IIIC, IIID, or IV melanoma at initial
presentation or subsequent recurrence. These participants have disease amenable to complete
surgical resection at the time of enrollment in the study. The resectable disease does not
need to be measurable by RECIST v1.1 criteria.
Cohort 3 (Adjuvant): Participants with stage IIIA, IIIB, IIIC, IIID or IV melanoma resected
to no evidence of disease. Participants must initiate therapy within 12 weeks of last
surgical resection and within 12 weeks of being rendered clinically free of disease by
non-surgical approaches Patients that have undergone ablative therapy to a metastatic
lesion (e.g. GKRS, radiofrequency ablation) that manifest no additional sites of disease at
enrollment are eligible for treatment on cohort 3
- - Participants must be eligible to be treated with BRAF inhibitor and MEK inhibitor
- - Participants with prior therapy with targeted therapies specific for mutated BRAF
including BRAF and/or MEK inhibitors are eligible provided that there was clinical
benefit to prior therapy with these agents as judged by the treating physician.
must be an interval of at least 6 months from the last BRAF/MEK therapy and enrollment
in this clinical study
- - Participants will be required to have radiological studies at baseline to establish
measurable disease for cohort 1 or to prove lack of distant metastases for cohorts 2
Required studies include:
- - Chest CT scan,
- Abdominal and pelvic CT scan, and
- Head CT scan or MRI
- Participants in cohorst 1 & 2 who have metastatic melanoma safely available for biopsy
pretreatment and on day 22 must consent to having those biopsies.
These metastases may
be in nodes, skin, soft tissue, liver, or other sites that can be accessed by needle
biopsy, incisional or excisional biopsy, with or without image guidance.
6 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
or systemic immunotherapy
- There has been no evident growth of any brain metastasis since the most recent
treatment if the last treatment is >4 weeks prior to enrollment
- No brain metastasis is > 2 cm in diameter at the time of registration
- Neurologic symptoms have returned to baseline off steroids,
- Subjects are not using steroids for at least 7 days prior to registration.
- - The most recent surgical resections or gamma-knife therapy for malignant melanoma
must have been completed ≥ 1 week prior to registration
- ECOG performance status of 0-2
- Participants must have the ability and willingness to give informed consent
- Laboratory parameters as follows:
- ANC > 1000/mm3
- Platelets > 100,000/mm3
- Hgb > 9 g/dL
- HgB-A1c ≤ 8.5%
- AST and ALT up to 2.5 x upper limits of normal (ULN).
Patients known to have
Gilbert's disease may be eligible with AST and ALT up to 5 x ULN.
- - Bilirubin up to 2.5 x ULN
- Alkaline phosphatase up to 2.5 x ULN.
- - Creatinine up to 1.5 x ULN
- Age 18 years or older at registration
- Participants must have at least two intact (undissected) axillary and/or inguinal
lymph node basins
- 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
- Corticosteroids, administered transdermally, parenterally or orally.
steroids (e.g.: Advair®, Flovent®, Azmacort®) are not permitted. Topical
corticosteroids are acceptable.
- - Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
- Interleukins (e.g. Proleukin®)
- Any investigational medication
- HIV positivity or evidence of active Hepatitis C virus.
- - Participants who are currently receiving nitrosoureas or who have received this
therapy 6 weeks prior to registration
- Participants who are currently receiving a checkpoint molecule blockade therapy, or
who have received this therapy within 3weeks prior to registration.
- - 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.
- - 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.
- - Participants with uncontrolled diabetes, defined as having a HgB-A1c greater than
- - 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
- - 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 3 years
- Participants with known addiction to alcohol or drugs who are actively taking those
agents, or participants with recent (within 1 year of registration) or ongoing illicit
IV drug use.
- - Body weight < 110 pounds
- Participants with a known history of glucose-6-phosphate dehydrogenase deficiency.