A Phase I Study With a Personalized NeoAntigen Cancer Vaccine in Melanoma

Inclusion Criteria (all must be met):

• Patient is willing and able to give written informed consent.
• Patient is agreeable to allow tumor and normal tissue samples to be submitted for complete exome and transcriptome sequencing.
• Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIB, IIIC, IVM1a, or IVM1b cutaneous melanoma (anatomic stages T1-4b N1a and T1-4b N2a not included). The current diagnosis may be the patient's first diagnosis of melanoma or recurrent melanoma after previous diagnosis of an earlier stage melanoma.
• Patients will undergo complete resection of their primary melanoma (if not already removed) and all regional metastatic disease with the intent of rendering them free of melanoma.
• The patient must be free of unresectable metastatic disease within 4 weeks prior to the surgery being performed with the intention to remove all melanoma.
• This pre-surgery baseline assessment must be documented by complete physical examination and imaging studies. Imaging studies must include a total body PET-CT in conjunction with a brain MRI (or head CT if brain MRI is contraindicated). If a PET/CT scan cannot be done, a CT of the neck, chest, abdomen, and pelvis should be performed.
• Patients may have received prior interferon alpha (IFN-α), but must have discontinued IFN-α therapy within 4 weeks prior to enrollment on the trial. Patients who have not received prior adjuvant therapy should be informed of the potential therapeutic benefit of IFN-α.
• Previous radiation therapy, including after the surgical resection, is allowed as long as 14 days have elapsed between the radiation and initiation of first vaccination with NeoVax.
• Age ≥ 18 years.
• ECOG performance status of 0 or 1
• Normal organ and bone marrow function as defined below:
• Leukocytes ≥ 3,500/mcL
• Absolute lymphocyte count > 800/mcL
• Absolute neutrophil count > 1,500/mcL
• Platelets > 100,000/mcL
• Hemoglobin > 10.0 g/dL
• Total serum bilirubin 2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from sexual activity throughout the study, starting with visit 1 through 4 weeks after the last dose of study therapy. Approved contraceptive methods include, for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
• Male patients must agree to use an adequate method of contraception starting with the first dose of NeoVax through 4 weeks after the last dose of study therapy.

Exclusion Criteria (one or more will exclude from participation):

• Prior treatment with immune-modulatory agents including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, CD137 stimulation with the exception of INF-α given as adjuvant treatment for high-risk, surgically resected melanoma
• Prior investigational, melanoma-directed, cancer vaccine therapy
• Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition
• Treatment with other investigational products within the last 2 months prior to entry into this study
• Previous bone marrow or stem cell transplant
• Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents; chronic use of systemic corticosteroids
• Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4 weeks prior to enrollment to the study. Patients may not receive any non-oncology vaccine therapy during the period of NeoVax administration and until at least 8 weeks after the last dose of study therapy
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases
• Mucosal melanoma or uveal melanoma are not