Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific
disease but it has been approved for other uses. Nivolumab is an antibody inhibitor of the
programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune
system to recognize and fight cancer.

In this research study, the investigators are investigating whether nivolumab has any
activity in patients who have a rising PSA (prostate specific antigen) after previously
undergoing surgery or radiation for prostate cancer. Although nivolumab was previously not
found to have significant effect in advanced prostate cancer after all other therapies had
failed, based on new research, the investigators are testing whether nivolumab could have a
greater effect earlier in the disease course and before patients receive hormone therapies.

Inclusion Criteria:

- Patients must have signed an informed-consent form indicating that the patient
understands the purpose of and procedures required for the study and is willing to
participate in the study.

- Patients must have a history of prostate adenocarcinoma (adenocarcinoma must be the
primary histology; secondary components of variant histologies are acceptable)
confirmed on biopsy and treated with primary radical prostatectomy (RP) or definitive
radiation (RT). Prior salvage RT is acceptable.

- Patients must have experienced biochemical recurrence (BCR) defined as:

- Following primary RP: Any detectable rising PSA after RP (or after salvage RT if
performed)

- Following primary RT: PSA rise to ≥2 ng/mL above the nadir

- No evidence of metastases on conventional imaging (CT or MRI plus bone scan)

- PSA doubling time (PSADT) <10 months --PSADT: calculated as per Prostate Cancer
Working Group 3 (PCWG3) and the Memorial Sloan Kettering Cancer Center calculator:
(https://www.mskcc.org/nomograms/prostate/psa_doubling_time)

With linear regression model of normal logarithm of PSA and time, based on:

- At least 3 consecutive PSA values with each value ≥0.2 ng/mL

- Interval between first and last PSA values is ≥8 weeks but ≤12 months

- Most recent PSA ≥2.0 ng/mL

- Archival tissue is mandatory, either prostatectomy specimen or (in patients who
received primary RT) diagnostic core biopsies. Patients must consent to
next-generation sequencing performed on this tissue.

- If diagnostic core biopsies are only available tissue, at least 3 cores must be
involved by tumor

- Easteron Cooperative Oncology Group (ECOG) performance status 0-1

- Age ≥18 years

- Adequate organ and marrow function:

- System Laboratory Value

- Hematological

- White blood cell (WBC) ≥ 2000/µL

- Absolute Neutrophil Count (ANC) ≥ 1500/μL

- Platelets (Plt) ≥ 100 x103/μL

- Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion)

-Renal

- Serum Creatinine ≤ 2 x ULN

- Hepatic

- Bilirubin1 ≤ 1.5× upper limit of normal (ULN)

- Aspartate aminotransferase (AST) ≤ 3 × ULN

- Alanine aminotransferase (ALT) ≤ 3 × ULN

- Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL

- Baseline testosterone ≥100 ng/dL

- Recovery from acute toxicity related to prior therapy, including surgery and
radiation, or no treatment-related toxicity ≥ grade 2.

- History of prior malignancy or concurrent separate malignancy is not an exclusion
criterion so long as the non-prostate malignancy is stable and does not require
any treatment.

- Able to understand and sign informed consent and adhere to study procedures.

- Male patients whose female partners are of reproductive potential must agree to
use a contraception during the trial period

Exclusion Criteria:

- Current use of ADT or plan to initiate ADT during trial period

- Major surgery or radiation therapy within 14 days of starting study treatment

- Subjects with active autoimmune disease. Patients with a history of autoimmune disease
that has not required systemic immunosuppressive therapy or does not threaten vital
organ function including central nervous system, heart, lungs, kidneys, skin, and
gastrointestinal tract will be allowed.

- Known history of immune deficiencies or chronic viral infections including HIV,
hepatitis B (HBV), and hepatitis C (HCV) (patients with prior therapy for HBV or HCV
is permitted if viral clearance was documented).

- Concurrent medical condition requiring use of systemic corticosteroids with prednisone
>10 mg per day or equivalent. Use of inhaled, nasal, and topical steroids (applied to
small body areas) is allowed.

- Current use (within past 4 weeks) of other prohibited medications including
anti-cancer therapies, hormonal therapies, 5-alpha reductase inhibitors, and
alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).

- Prior treatment with immune checkpoint inhibitors. (Prior cancer vaccines are
allowed.)

- Serious intercurrent medical or psychiatric illness that, in the judgment of the
investigator, would interfere with patient's ability to carry out the treatment
program