This study evaluates whether it is safe to administer a peptide vaccine made of 6MHP and a
mutated neoantigen peptide (BRAF585-614-V600E) combined with adjuvants. The adjuvants that
will be used in this trial are a CD40 antibody (CDX-1140) and a toll-like receptor (TLR) 3
agonist (Poly-ICLC). The study will also investigate the effects of the vaccine and the
adjuvants on the immune response. The investigators will monitor these effects by performing
tests in the laboratory on participants' blood and skin tissue.
Main Inclusion Criteria:
1. a. For individuals with primary cutaneous, mucosal, or unknown melanoma, an individual
must have stage IB ulcerated, II, III, or IV melanoma at original diagnosis or at
restaging after recurrence, and be rendered clinically free of disease by surgery,
other therapy, or spontaneous remission within 6 months prior to registration.
b. For patients with stage II, III, or IV uveal melanoma, patients must be rendered
clinically free of disease by surgery, other therapy, or spontaneous remission within
6 months prior to registration.
2. An individual with small radiologic or clinical findings of an indeterminate nature
may still be eligible
3. An individual may have had cutaneous, uveal, mucosal primary melanoma, or an unknown
4. An individual must have at least 6-10 nevi at least 4 mm in diameter that are located
on truncal or non-acral extremity sites and are accessible for biopsy and observation.
5. Diagnosis of melanoma must be confirmed by cytological or histological examination.
6. Individuals will be required to have radiological studies to rule out radiologically
evident melanoma metastasis.
7. Individuals who have had brain metastases will be eligible if all of the following are
- Each brain metastasis must have been completely removed by surgery or each
unresected brain metastasis must have been treated with stereotactic
- No brain metastasis is > 2 cm in diameter at the time of registration.
- Any neurologic symptoms attributable to brain metastases have returned to
- There is no evidence of new or enlarging brain metastases.
8. The most recent surgical resections or gamma-knife therapy for malignant melanoma must
have been completed ≥ 1 week and ≤ 6 months prior to registration.
9. ECOG performance status of 0 or 1 (Section 13.3).
10. Ability and willingness to give informed consent.
11. Adequate organ function as determined by laboratory parameters.
12. Male or female, age 18 years or older at registration.
13. Individuals must have at least two intact (undissected) axillary and/or inguinal lymph
14. For females and males of reproductive potential: agreement to use adequate
contraception during study participation and for an additional 3 months after
receiving the last dose of study drug.
Main Exclusion Criteria:
1. Individuals who have received the following medications or treatments at any time
within 4 weeks of registration:
- 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 some qualifications and exceptions
- Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
- Interleukins (e.g. Proleukin®)
- Any investigational medication
- Targeted therapies specific for mutated BRAF or for MEK
2. Individuals who are currently receiving nitrosoureas or who have received this therapy
within 6 weeks of registration.
3. Individuals who are currently receiving a checkpoint molecule blockade therapy, or who
have received this therapy within 12 weeks of registration.
4. Individuals with known or suspected allergies to any component of the vaccine.
5. Individuals who have received prior melanoma vaccinations with 6MHP plus the mutated
BRAF peptide. However, participants who have received prior vaccinations will be
eligible to enroll 12 weeks following their last vaccination if they have recurred
during or after administration of the vaccine, and if their vaccines did not include
all of the synthetic peptides included in this protocol.
6. Individuals who have previously received CDX-1140 or another CD40 agonistic antibody.
7. Pregnancy. Female individuals of childbearing potential must have a negative pregnancy
test (urinary or serum beta-HCG) obtained within 2 weeks prior to registration.
8. HIV positivity or evidence of active Hepatitis C virus (testing to be done within 6
months of study entry).
9. Female individuals must not be breastfeeding.
10. Individuals in whom there is a medical contraindication or potential problem in
complying with the requirements of the protocol in the opinion of the investigator.
11. Individuals classified according to the New York Heart Association classification as
having Class III or IV heart disease (Section 13.4).
12. Individuals must not have had prior autoimmune disorders requiring systemic cytotoxic
or immunosuppressive therapy, or autoimmune disorders with visceral involvement.
Participants with an active autoimmune disorder requiring these therapies are also
excluded. Some autoimmune disorders 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 non-steroidal anti-inflammatory drugs (NSAID)
- Resolved childhood asthma/atopy
- Endocrinopathies on stable hormone replacement therapy
13. Individuals 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.
14. Individuals with current pneumonitis. Individuals must not have had pneumonitis within
30 days of registration. Patients who have had complete resolution of prior
pneumonitis will be eligible.
15. Individuals who have received a live vaccine within 30 days of registration.
16. Body weight < 110 pounds (50 kg) at registration