Vaccine Therapy in Treating Patients with Stage IIIB-IV Melanoma

Inclusion Criteria

• 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, and IV M1a and b 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
• Complete surgical resection of metastatic disease (lymph node, in transit, satellite lesion[s], distant metastases) with negative margins on resected specimens as confirmed by pathologic review has not been performed, but is deemed feasible by the treating surgical oncologist; surgical resection of the primary melanoma may or may not have been performed
• 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 positron emission tomography (PET)-computed tomography (CT) in conjunction with a brain magnetic resonance imaging (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-alpha), but must not have received IFN-alpha in the 4-week period prior to enrollment on the trial; patients who have not received prior adjuvant therapy should be informed of the potential therapeutic benefit of IFN-alpha; 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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• 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 =< 1.0 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional upper limit of normal
• Serum creatinine =< 1.5 x institutional upper limit of normal
• Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent of human chorionic gonadotropin [HCG]) before entry onto the trial and within 7 days prior to start of study medication; it is the investigators’ responsibility to repeat the pregnancy test should start of treatment be delayed
• Female patients enrolled in the study, who are not free from menses for > 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; intrauterine 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

• Prior treatment with immune-modulatory agents including, but not limited to: interleukin (IL)-2, cytotoxic T-lymphocyte antigen 4 (CTLA)-4 blockade, programmed death (PD-1)-1/programmed death-ligand 1 (PD-L1) blockade, cluster of differentiation (CD)40 stimulation, CD137 stimulation with the exception of INF-alpha given as adjuvant treatment for high-risk, surgically resected melanoma
• Prior investigational melanoma-directed cancer vaccine therapy
• Prior chemotherapy, including targeted therapy such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or mitogen-activated protein kinase kinase (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 during the 4 week period prior to first dose of NeoVax administration; 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 and uveal melanoma are not allowed
• Active, known, or suspected autoimmune disease or immunosuppressive conditions with the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism requiring hormone replacement, or psoriasis not requiring systemic treatment
• Concomitant treatment with corticosteroids greater than physiologic doses (used in the management of cancer or non-cancer-related illnesses); topical (if not including the proposed vaccination sites) or inhalational steroids are allowed
• Known chronic infections with human immunodeficiency virus (HIV), hepatitis B or C
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of adverse events (AEs)
• Pregnant women are excluded from this study; nursing women are excluded from this study
• Individuals with a history of an invasive malignancy except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with any of the following cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral cavity or cervix and basal cell or squamous cell carcinoma of the skin