Pembrolizumab +/- SD-101 in Hormone-Naïve Oligometastatic Prostate Cancer With RT and iADT

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial.
• Be >=18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Histologically documented adenocarcinoma of the prostate
• Oligometastatic disease. In order to be eligible, the participant must have a total of 2 ng/mL at baseline or prior to initiation of hormonal therapy
• Baseline testosterone >150 ng/dL if participant has not initiated hormonal therapy, for those participants who have already initiated hormonal therapy, baseline testosterone is not required
• Consent to undergo mandatory prostatic core biopsies at the time of fiducial marker placement and 1-3 weeks after Cycle 1 Day 1 of pembrolizumab.
• The effects of pembrolizumab on the developing human fetus is unknown. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the first dose of study therapy, for the duration of the study participation, and for 120 days after the last dose of study therapy. Their partners should also be encouraged to use proper method of contraception. Their partners should also be encouraged to use proper method of contraception.
• Demonstrate adequate organ function defined as: Adequate Organ Function Laboratory Values (Performed within 10 days of treatment initiation):
• Absolute neutrophil count (ANC) ≥1, 500 /microliter (mcL)
• Platelets >=100,000 / mcL
• Hemoglobin >=9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) 1.5 X institutional ULN. Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin 1.5 ULN
• Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin >2.5 mg/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT)
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Creatinine clearance should be calculated per institutional standard.

Exclusion Criteria

• Participants who are not appropriate candidates for prostate or oligometastasis-directed SBRT
• Participants with neuroendocrine or small cell features are not eligible.
• Participants with evidence of liver metastasis are excluded.
• Gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists (e.g., leuprorelin, degarelix) for > 2 months prior to consenting
• Antiandrogens (e.g., bicalutamide, flutamide, nilutamide, abiraterone, enzalutamide) for > 2 months prior to consenting. Participants on 5-alpha reductase inhibitors are allowed on study.
• Estrogen containing compounds for > 2 months prior to consenting
• PC-SPES or PC-x products. Other herbal therapies or supplements will be considered by the Principle Investigator on a case-by-case basis based on their potential for hormonal or anti-cancer therapies.
• Prior immunotherapy or chemotherapy for prostate cancer
• Prior radiation therapy to the prostate
• Prior prostatectomy
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment, with the exception of steroids for adrenal insufficiency in which case