T-Cell Responses to Neoantigens Post Treatment With Ipilimumab in Men With Metastatic Castration-Resistant Prostate Cancer

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive ipilimumab by
vein over about 90 minutes at Weeks 1, 4, 7, and 10. Your blood pressure will be measured
every 30 minutes during the infusion, as well as an hour after you are finished receiving the
study drug.

You will continue to receive your current hormone therapy as scheduled.

You will be given standard drugs (such as steroids) to help decrease severe side effects. You
may ask the study staff for information about how the drugs are given and their risks.

Study Visits:

You will have a study visit before each dose of ipilimumab, then every 4 weeks for a total of
3 visits after the last dose of ipilimumab. At each of these visits, the following tests and
procedures will be performed:

- You will have a physical exam.

- Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood
will also be used and to measure your protein, PSA levels.

- Blood (up to 7 tablespoons) and urine will be collected to test for biomarkers. (Weeks
7, 14, and 22 only)

- Blood (about 1½ teaspoons) will be drawn to check your testosterone level. (Week 10
only)

- Blood (up to 10 tablespoons) will be drawn to test your immune system. You will sign a
separate consent form for this blood draw.

At Weeks 14 and 22, the following tests and procedures will be performed to check the status
of the disease:

- You may have a chest x-ray.

- You will have CT scans or MRIs of the abdomen, pelvis. If the doctor thinks it is
needed, you will also have a CT scan of the chest. If a CT scan of the chest is done, a
chest x-ray is not required.

- You will have a bone scan.

If the study doctor thinks it is needed, you may have additional bone scans or CT scans or
MRIs of the abdomen, pelvis, or chest to check the status of the disease.

Length of Study:

You may receive the study drug for up to 10 weeks. You will remain on study (receiving your
standard hormone therapy) for up to a total of 22 weeks. You will be taken off study
treatment if you have intolerable side effects, if the disease gets worse, or if you are
unable to follow study directions. If you develop certain side effects or have certain side
effects for a long period of time, you may be taken off study. The study doctor will let you
know if you need to be taken off study.

Inclusion Criteria:

1. Signed written Informed Consent for this protocol.

2. Agreed to participate in laboratory protocol PA13-0291 for the testing of biomarkers
as described in this clinical protocol.

3. Patients included in the study must be >/= 18 years old.

4. Histologically or cytologically confirmed carcinoma of the prostate.

5. Subjects must have metastatic prostate cancer mass tissue collection within 3 months
of study entry.

6. Evidence of metastatic disease on previous bone scan, CT scan and/or MRI.

7. Asymptomatic or minimally symptomatic.

8. Tumor progression while on hormone therapy with castrate levels serum testosterone
( criteria according to the Prostate Cancer Working Group 2 (PCWG2).Castrate levels of
testosterone must be maintained by surgical or medical means throughout the conduct of
the study.

9. ECOG performance status
10. Patients must have normal organ and marrow function as defined below: a) WBC >/=
2500/uL.; b) ANC >/= 1000/uL.; c) Platelets >/= 75 x 10^3/uL.; d) Hemoglobin >/= 9
g/dL.; e) Creatinine metastases. For patients with liver metastasis ALT Bilirubin total bilirubin
11. Patient agrees to use adequate contraception (barrier method of birth control) prior
to study entry, during therapy and up to 3 months after last dose of ipilimumab.

Exclusion Criteria:

1. Treatment with any of the following medications or interventions concomitantly or
within 28 days of starting ipilimumab: a.) Systemic corticosteroids. Use of inhaled,
intranasal, intra-articular and topical steroids is acceptable, as is a short course
(i.e. CT scans.; b.) External beam radiation therapy or major surgery requiring general
anesthetic.; c.) Any systemic therapy for prostate cancer (with the exception of
bisphosphonates and RANK-ligand inhibitors for bone metastases which are allowed)
including chemotherapy, secondary hormonal therapies (such as megestrol acetate,
diethylstilbestrol, ketoconazole, abiraterone, enzalutamide) and non-steroidal
anti-androgens (such as bicalutamide, flutamide or nilutamide).; d.) Immune
modulators, cytokines or vaccines for the management of cancer or non-cancer-related
illnesses.;

2. (Exclusion Criteria #2 Cont.): e.) Any non-oncology vaccine therapy used for
prevention of infectious diseases (for up to one month before any dose of
ipilimumab).; f.) Any other investigational product.

3. Use of controlled schedule III controlled substances for cancer-related pain control.

4. Autoimmune disease: Patients with a history of inflammatory bowel disease (including
Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid
arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus
or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this
study.

5. Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of AEs, such as a condition associated with frequent diarrhea.

6. Patients with known brain metastases.

7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, history of congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

8. Known HIV, Hepatitis B, or Hepatitis C.

9. Untreated symptomatic spinal cord compressions.

10. Other malignancies requiring active therapy or known to be associated with altered
immune response.

11. Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI
obstruction and abdominal carcinomatosis which are known risk factors for bowel
perforation.