Nivolumab in Biochemically Recurrent dMMR Prostate Cancer

Inclusion Criteria

• Willing and able to provide signed informed consent and HIPAA authorization for the release of personal health information
• Males aged 18 years and above
• Prior local therapy with prostatectomy or EBRT/brachytherapy is required
• Prior salvage or adjuvant radiation therapy is allowed but not mandated. Radiation therapy must have been completed for at least 6 months.
• Absolute PSA >=1.0 ng/mL at screening
• Must have at least one of the following genetic alterations identified using archival tissue (i.e. prostate needle biopsy prior to radiation therapy or prostatectomy specimen):
• Microsatellite instability (MSI-high) status by clinical grade testing
• MMR protein loss (MSH2, MSH6, MLH1, PMS2) by immunohistochemistry
• Inactivating mutation of MSH2, MSH6, MLH1 or PSM2 by clinical grade genomic testing
• Tumor mutational burden >= 20 mutations/megabase (TMB >=20 muts/Mb) by clinical grade testing
• Inactivating mutation (at least monoallelic of CDK12 by clinical grade testing
• Serum testosterone >= 150 ng/dL
• No radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 4 weeks.
• Karnofsky Performance Status (KPS) >= 70% within 14 days before start of study treatment (ECOG = 9.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) >= 1.0x10^9 / L
• Platelet count >= 100 x 10^9 /L
• Total bilirubin within institutional upper limit of normal (ULN) (in patients with Gilbert's syndrome, total bilirubin =40 mL/min:

Estimated creatinine clearance = [(140 - age (years)) x weight (kg)] / [serum creatinine (mg/dL) x 72]

• Participants must have a life expectancy of >= 6 months
• Male participants and their partners who are sexually active and of childbearing potential must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 7 months after the last dose of nivolumab to prevent pregnancy in a partner.
• No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)

Exclusion Criteria

• Metastatic disease or currently active second malignancy
• Prior androgen deprivation therapy (ADT) in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary; prior ADT for biochemical recurrence is allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (>150 ng/dL)
• Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) within the past 2 weeks is not permitted. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
• Involvement in the planning and/or conduct of the study (applies to both BMS staff and/or staff at the study site)
• Participation in another clinical study with an investigational product during the last 4 weeks/28 days
• Patients should be excluded if they have had prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
• Patients should be excluded if they have an active, known or suspected autoimmune disease (e.g. inflammatory bowel disease, rheumatoid arthritis, autoimmune hepatitis, lupus, celiac disease). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recure in the absence of an external trigger.
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone daily equivalents) or other immunosuppressive medications within 14 days of study dru