Checkpoint Inhibitors and SBRT for MCRPC

Inclusion Criteria: 1. Have a signed Independent Ethics Committee (IEC)-approved informed consent form prior to any study-specific evaluation. Subjects must be willing and able to comply with scheduled visits, treatment schedule, lab testing and other requirements of the study. 2. Male ≥18 years of age at the time consent form is signed 3. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed) 4. If possible, metastases accessible for image-guided percutaneous biopsy should be performed, if considered safe assessed by the PI. 5. Surgically or medically castrated, with serum testosterone levels \<50 ng/dL (1.73 nM). For patients currently being treated with luteinizing hormone-releasing hormone (LHRH) agonists (i.e., patients who have not undergone an orchiectomy) therapy must be continued throughout the study 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 7. Life expectancy greater than 3 months 8. Evidence of disease progression after prior therapy for mCRPC: 1. Disease progression after treatment with 1 androgen-receptor (AR) targeted therapies (abiraterone acetate, enzalutamide or investigational AR-targeted drug) for castrate-resistant disease AND 2. Disease progression after treatment with 1 line of taxane-based chemotherapy for castration resistant disease. Prior taxane therapy administered for hormone sensitive disease is permitted and is not counted toward this limit. Disease progression after initiation of most recent therapy is based on any of the following criteria: i. Rise in PSA: a minimum of 2 consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2ng/mL j. Transaxial imaging: New or progressive tumor on CT or MRI scans as defined by RECIST 1.1 or new lesions on bone scan per PCWG3. 9. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to the first dose of immunotherapy with nivolumab and ipilimumab: a. Bone marrow function: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelets \> 100 x 109/L iii. Hemoglobin ≥ 9 g/dL (5.6 mmol/L) independent of transfusion within 14 days b. Hepatic function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN). For patients with liver metastases AST and ALT \< 5 x ULN ii. Bilirubin \< 1.5 x ULN c. Renal function: Serum creatinine \< 1.5 x ULN d. Coagulations status: International Normalized Ratio (INR) ≤ 1.5 10. Male patients with female partners of childbearing potential may be enrolled if they are: 1. Documented to be surgically sterile (ie, vasectomy): or 2. Committed to practicing true abstinence during treatment and for 4 months after the last dose of immunotherapy; or 3. Committed to using any contraception method with a failure rate of less than 1% per year of contraception (refer to protocol) with their partner during treatment and for 4 months following last dose of immunotherapy. Exclusion Criteria: 1. Active malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer * Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to be enrolled in the trial provided all chemotherapy was completed \> 6 months prior and/or bone marrow transplant \> 2years prior to first dose of ipilimumab and nivolumab 2. Prior therapy with an anti-programmed cell death protein 1 (anti-PD1), anti-programmed death-ligand 1 (anti-PD-L1), anti-CD137 or anti-CTLA4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 3. Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable (i.e., not requiring steroids for at least 4 weeks prior to first dose of ipilimumab and nivolumab and have had appropriate scans screening assessments) 4. Symptomatic or impending spinal cord compression unless appropriately treated, clinically stable and asymptomatic 5. If patient have an active known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger 6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or history of chronic hepatitis B or C 7. Received treatment with chemotherapy, hormonal therapy (with the exception of LHRH analog), radiation, antibody therapy or immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors or experimental drugs within 4 weeks prior to first dose of ipilimumab and nivolumab 8. Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor 9. Initiated denosumab or bisphosphonate therapy or adjusted denosumab or bisphosphonate dose/regimen within 4 weeks prior to first dose of ipilimumab and nivolumab. Patients on stable denosumab or bisphosphonate regimen are eligible and may continue treatment 10. Non-study related minor surgery procedure \<5 days or major surgery \< 21 days prior to first dose of ipilimumab and nivolumab; in all cases the patient must be sufficiently recovered and stable before treatment administration 11. Presence of auto-immune diseases 12. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and in the opinion of the investigator would make the patient inappropriate for entry into the study 13. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids ( \>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease 14. As there is a potential risk for hepatic toxicity with nivolumab/ipilimumab combinations, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab/ipilimumab containing regimen 15. Allergies 1. History of allergy to study drug components 2. History of severe hypersensitivity reaction to any monoclonal antibody