Pilot Study of Vigil™ + Pembrolizumab for Advanced Melanoma

Tissue Procurement Inclusion Criteria: Patients will be eligible for tissue procurement for the Vigil™ manufacturing process, if they meet all of the following criteria: 1. Age ≥ 18 years. 2. ECOG Performance Status ≤ 1 3. Estimated survival ≥ 6 months. 4. If activating BRAF mutation present, subject has previously received BRAF and/or MEK inhibitor 5. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of \~10-30 grams tissue ("golf-ball" size) for vaccine manufacture. Tissue obtained for vaccine manufacture must not have been previously irradiated. 6. At least one area of cancer that is not intended for resection or vaccine manufacture and in the opinion of the investigator is appropriate for serial biopsy. 7. Ability to understand and the willingness to sign a written informed consent document for tissue harvest. Tissue Procurement Exclusion Criteria: Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil™ manufacturing: 1. Documented history of tumor PD-L1 expression positivity (defined as membranous staining of neoplastic cells \>1%) 2. Anti-cancer chemotherapy, immunotherapy, or biologic therapy within 3 weeks or radiation therapy within 1 week prior to procurement of tumor for vaccine manufacture. 3. Radiation therapy treatment of lesion intended for vaccine manufacture unless post-radiation progression of that lesion is confirmed. 4. Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for \< 30 days duration 5. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected. 6. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months. 7. Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids. 8. Known history of allergies or sensitivities to gentamicin. 9. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator. 10. Known HIV or chronic Hepatitis B or C infection. 11. History of pneumonitis or interstitial lung disease. Study Enrollment Inclusion Criteria: Patients will be eligible for registration into the trial if they meet all of the following inclusion criteria: 1. Successful manufacturing of at least 4 vials of Vigil™. 2. ECOG performance status (PS) ≤ 1 3. Estimated survival ≥ 4 months. 4. Adequate organ function as defined by the following laboratory values: * Hematological Absolute granulocyte count ≥ 1,500/mm3 * Hematological Absolute lymphocyte count ≥ 500/mm3 * Hematological Platelets ≥ 75,000/mm3 * Hematological Hemoglobin ≥ 9 g/dL * Renal Creatinine ≤ 1.5x institutional upper limit of normal * Hepatic Total bilirubin ≤ 1.5x institutional upper limit of normal * Hepatic AST(SGOT) and ALT(SGPT) ≤2x institutional upper limit of normal or ≤5x institutional upper limit of normal if liver metastases * Coagulation INR / PT and aPTT ≤ 1.5 x ULN (if not using anticoagulants)\*If patient receiving anticoagulant therapy value must be within therapeutic range for the condition being treated. * Immunological Thyroid Stimulating Hormone within institutional limits\*\*If TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed. 5. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade \> 2 or better. 6. If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. 7. Patient has agreed to provide on study tumor biopsies for correlative research. 8. Ability to understand and the willingness to sign a written informed protocol specific consent. Study Enrollment Exclusion Criteria: In addition to the procurement exclusion criteria, patients will NOT be eligible for study registration and enrollment if meeting any of the following criteria: 1. Any anti-neoplastic therapy between tissue procurement for vaccine manufacture and start of study therapy. 2. Live vaccine used for the prevention of infectious disease administered \< 30 days prior to the start of study therapy. 3. Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or make it not in the best interest of the patient to participate.