Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer

Inclusion Criteria: For a subject to be eligible for participation in this study, all of the following criteria must be satisfied: 1. Patients must have histologically confirmed adenocarcinoma of the prostate without previous therapy for prostate cancer (PC). * Treatment-naïve AND * Undergoing radical prostatectomy (RP) as initial, locally definitive therapy for PC and * Eligible for RP in a 3 month timeframe AND * Consentable for RP 2. Subject's archival prostate biopsy specimen is available, and subject consents to provide tissue for study endpoint analysis. The prostate biopsy slides or blocks must be available prior to starting any study treatment. 3. Age ≥ 18 years 4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Subject has adequate organ function, defined as: * White blood cell (WBC) count ≥ 3,000/microliter (mcL) * Absolute neutrophil count (ANC) ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Hemoglobin (Hgb) ≥ 10.0 g/dL * Creatinine ≤ 1.5x institutional upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x institutional ULN * Alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN * Aspartate aminotransferase (AST) ≤ 1.5 x institutional ULN * Prothrombin time (PT) /International Normalized Ratio (INR), partial thromboplastin time (PTT) within institutional ULN 6. No known history of human immunodeficiency virus (HIV) 1 and 2, human T-cell lymphotropic virus (HTLV)-I/II, and Hepatitis B and C. 7. Ability to understand a written informed consent document, and the willingness to sign it. 8. Because of the unknown potential risk to a gamete and/or developing embryo from these investigational therapies, subjects must agree to use adequate contraception (i.e. barrier method) for the duration of study participation, and for three months after discontinuing therapy. Exclusion Criteria: A subject will not be eligible for participation in this study if any of the following criteria apply. 1. Subject's biopsy specimen reveals neuroendocrine or small cell features. 2. Subject has any evidence of metastatic disease (pre-operative staging will be undertaken per urologic standard of care) as deemed by the Investigator. 3. Subject has prior use of any hormones, including luteinizing hormone-releasing hormone (LHRH) agonists, ketoconazole, antiandrogens (such as bicalutamide, flutamide, or nilutamide), or 5-α-reductase inhibitors. 4. Subject has prior use of any anti-cancer treatment or product, such as PC-SPES (or any other PC-x product: PC-HOPE, PC-CARE, PC-PLUS, etc). 5. Subject has received prior radiation therapy or chemotherapy for prostate cancer. 6. Chronic administration (defined as daily or every other day for continuous use \>14 days) of systemic corticosteroids within 28 days of the first planned dose off PROSTVAC-V/F. Use of inhaled steroids, nasal sprays, and topical creams for small body areas are allowed. 7. Active atopic dermatitis or skin condition that disrupts the epidermis 8. Inflammatory eye disease requiring steroid treatment 9. History of prior solid organ or bone marrow transplant 10. Previous history of hypersensitivity to eggs or allergy or untoward reaction to prior vaccinia (smallpox) vaccination. 11. Splenectomy 12. Subject, or subject's close household contacts (defined as those who share housing or have close physical contact) have any of the following conditions during the screening and/or treatment periods: * active or a history of atopic dermatitis, eczema or other eczematoid skin disorders that disrupt the epidermis * other acute, chronic or exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves * pregnant or nursing * immunodeficient or immunosuppressed (by disease or therapy), including HIV infection 13. Subject's close household contacts include children less than the age of three 14. History of, or active autoimmune disease (e.g., autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogren´s syndrome, scleroderma, myasthenia gravis, Goodpasture´s syndrome, Addison´s disease, Hashimotos´s thyroiditis, or Graves disease) as determined by the treating medical oncologist. * Persons with vitiligo are not excluded. * Diabetics are not excluded if the condition is well controlled: 1. Hemoglobin A1C \< 7.0, and 2. No evidence of end-organ damage due to diabetes, such as diabetic retinopathy, nephropathy, or neuropathy 3. Persons with type 2 diabetes are not excluded since this is not an autoimmune disease, and do not need to meet these criteria. * Persons with hypothyroidism are not excluded if condition is well controlled, and condition is due to a non-autoimmune etiology. 15. Subject has received treatment with any investigational immunotherapy within 2 years prior to study screening or has received treatment with any other investigational product within 28 days prior to study screening. 16. Subject has participated in any previous study involving PROSTVAC-V/F, Sipuleucel-T or ipilimumab, regardless of whether the subject received PROSTVAC-V/F, Sipuleucel-T or ipilimumab. 17. Subject has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PROSTVAC-V/F or ipilimumab. 18. Subject has a history of stage III or greater cancer, excluding prostate cancer. Subjects with a history of basal or squamous cell skin cancers are allowed, provided that the subject was adequately treated and is disease-free at the time of study screening. Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years prior to study screening. 19. Subject has any uncontrolled, concurrent illness including, but not limited to the following: ongoing or active infection (bacterial, viral, or fungal), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, stroke or myocardial infarction within 6 months, or psychiatric illness that would limit compliance with study requirements. 20. Subject requires any medical intervention(s) or has any other condition(s) that, in the Investigator's opinion, will 1) make the administration of PROSTVAC or ipilimumab hazardous, 2) obscure the interpretation of adverse events (AEs), 3) compromise adherence with study requirements, or 4) otherwise compromise the study's objectives. 21. Subject has high-risk features (e.g., based on Gleason score, PSA, clinical stage, % positive biopsies), and the treating physician feels the subject should undergo radical prostatectomy sooner than planned within the protocol.