Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy

Inclusion Criteria:

- Provision of signed and dated informed consent form.

- Stated willingness to comply with all study procedures and availability for the
duration of the study.

- Male, aged ≥ 18 years

- ECOG Performance Status: 0-1

- Diagnosed with Grade Group 5 prostate cancer (PCa): Gleason grade 9 (4+5 or 5+4) or 10
(5+5) with >30% of cores involved; Any PSA or T-stage

- Pathologically (histologically) proven diagnosis of PCa undergoing their first line of
treatment

- Biopsy specimen available

- Patients with oligometastaic disease (defined as ≤3 sites of distant metastatic
disease, and/or positive lymph nodes confined to the pelvis) being treated with
curative intent are eligible for study participation

- Eligible for definitive RT (HDR + EBRT) + short-term ADT

- Undergoing radiation treatment at Moffitt Cancer Center

- Must have normal organ function

- Males who are sexually active with women of childbearing potential must agree to
follow instructions for method(s) of contraception for the duration of treatment with
study drug plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days
(duration of sperm turnover) for a total of 31 weeks post-treatment completion;
Azoospermic males are exempt from contraceptive requirements; Male participants must
be willing to refrain from sperm donation during the entire study and for 5 half-lives
of study drug plus 90 days (duration of sperm turnover).

Exclusion Criteria:

- Autoimmune disease: patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive
sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,
Wegener's Granulomatosis]) and motor neuropathy considered to be of autoimmune origin
(e.g., Guillain-Barre Syndrome and Myasthenia Gravis). Patients with Hashimoto's
thyroiditis are eligible to go on study. Active, known, or suspected autoimmune
disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent
immunosuppressive treatment are excluded. Patients with type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo,
psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected
to recur in the absence of an external trigger are permitted to enroll

- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days of study
entry. Corticosteroids with minimal systemic absorption (inhaled or topical steroids)
and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are
permitted in the absence of active autoimmune disease

- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody (including ipilimumab or any other antibody or drug specifically targeting T
cell co-stimulation or checkpoint pathways)

- Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected drug-related pulmonary toxicity

- Previous malignancies (except non-melanoma skin cancers, and the following in situ
cancers: bladder, gastric, colon, melanoma, or breast) unless a complete remission was
achieved at least 2 years prior to study entry AND no additional therapy is required
during the study period

- Known medical condition that, in the investigator's opinion, would increase the risk
associated with study participation or study drug(s) administration or interfere with
the interpretation of safety results

- Major surgery or significant traumatic injury that is not recovered at least 14 days
before the initiation of prostate radiation therapy

- Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or
positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
antibody test indicating acute or chronic infection

- Individuals with a positive test for HCV antibody but no detection of HCV RNA
indicating no current infection are eligible

- Known medical history of testing positive for human immunodeficiency virus (HIV) or
known medical history of acquired immunodeficiency syndrome (AIDS)

- Inadequate hematologic function; hepatic function; pancreatic function

- History of allergy or hypersensitivity to any of the study drugs or study drug
components.

- Uncontrolled intercurrent illnesses including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
psychiatric illness.

- Social situations that could limit the patient's compliance with study requirements.