PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

• INCLUSION CRITERIA:

For the neoadjuvant cohort, patients must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis. If evaluable tissue is not available, the patient must agree to undergo a pre-vaccination prostate biopsy on study. For the castration-resistant prostate cancer (CRPC) lead in cohort, if histopathological documentation is unavailable, a rising prostate specific antigen (PSA) and a clinical course consistent with prostate cancer would be acceptable.

• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PROSTVAC in combination with nivolumab, ipilimumab or both in participants 1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria). If participants had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal.
• Participants must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
• For all neoadjuvant cohorts:
• Participants must be a surgical candidate for radical prostatectomy based on standard workup of PSA, biopsy results, and if necessary supplemental imaging.
• Participants must have chosen radical prostatectomy as their definitive treatment of choice for management of their prostate cancer.
• No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent intravenous (IV) contrast, allergic reaction or anaphylaxis (in patients who have known contrast allergies) are allowed.

EXCLUSION CRITERIA

• Prior splenectomy.
• The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts (Close household contacts are those who share housing or have close physical contact):
• persons with active or a history of eczema or other eczematoid skin disorders
• those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves
• pregnant or nursing women; children under 3 years of age
• Participants should have no evidence, as listed below, of being immunocompromised:
• Human immunodeficiency virus (HIV) positivity due to the potential for decreased tolerance and risk for severe side effects.
• Hepatitis B or C positivity.
• Concurrent use of systemic steroids or steroid eye drops. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal, topical, or inhaled steroid use is permitted.
• Participants with known allergy to eggs or to compounds with a similar chemical or biologic composition to PROSTVAC, ipilimumab or nivolumab.
• No prior immune checkpoint inhibitors (e.g., anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) are allowed.
• Other serious intercurrent illness.
• Participants with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.
• Participants with significant autoimmune disease that is active or potentially life threatening if activated.
• Participants with clinically significant cardiomyopathy requiring treatment.
• Participants with ongoing toxicities related to prior therapies targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody are