Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

Inclusion Criteria

• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All patients must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study
• Patients may or may not have been treated previously with a nonsteroidal antiandrogen; for patients previously treated with an antiandrogen, they must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration; moreover, subjects who demonstrate an anti-androgen withdrawal response, defined as a >= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal
• Patients must have a castrate serum level of testosterone ( = 2.0 ng/mL
• Measurable disease: >= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion
• Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan (or fluorine F 18 sodium fluoride [NaF] PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging [MRI])
• Prior treatment with abiraterone or enzalutamide is permitted, but patients must have been off prior corticosteroid treatment for at least 3 months
• Life expectancy of at least 6 months
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• White blood cells (WBC) >= 2000/mm^3
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Hemoglobin (HgB) >= 9.0 gm/dL
• Platelets >= 100,000/mm^3
• Creatinine = = 3 years are eligible
• Patients with known brain metastases
• Any antibiotic therapy or evidence of infection within 1 week of registration
• Any other medical intervention or condition, which, in the opinion of the PI or treating physician, could compromise patient safety or adherence with the study requirements (including biopsies or leukapheresis procedures) over the primary 3-6 month treatment period
• Patients cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies

NOTE: There is no exclusion for prior immune-based therapy. This includes patients previously treated on Arms 1 or 2 who are otherwise eligible for treatment on Arm 3 or 4.