Tremelimumab + Durvalumab Chemotherapy Naive CRPC

Study Drug Administration:

Each study cycle is 28 days.

If you are found to be eligible to take part in this study, you will receive tremelimumab by
vein over 60 minutes on Day 1 of Cycles 1-4. You will not receive tremelimumab after Cycle 4.
You will also receive durvalumab by vein over about 60 minutes on Day 1 of Cycles 1-13.

On Day 1 of Cycle 1, you will stay in the clinic for about 1 hour after your dose of study
drugs to be watched for any side effects. After that, depending on what the study doctor
thinks is in your best interest, you may only need to stay in the clinic for about 30 minutes
after the dose.

On days that you receive both tremelimumab and durvalumab on the same day, you will receive
tremelimumab, wait about 1 hour, and then receive durvalumab.

You may receive palliative radiation therapy as part of your standard care while taking part
in this study. The study staff will discuss this option with you.

Length of Treatment:

You may receive up to 4 cycles of tremelimumab and up to 13 cycles of durvalumab. You may no
longer be able to take the study drugs if the disease gets worse, if intolerable side effects
occur, or if you are unable to follow study directions.

Retreatment:

Depending on how you respond to the study drugs and what the study doctor thinks is in your
best interest, you may be able to receive an additional 13 cycles of treatment as described
above (durvalumab and tremelimumab for 4 cycles and then 9 cycles of durvalumab alone). This
is called retreatment. If you take part in retreatment, you will sign this informed consent
form again.

Study Visits:

On Day 1 of every cycle:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests and to check your PSA levels.

Every 8 weeks for the first 48 weeks and then every 12 weeks after that, you will have a bone
scan and either an MRI or CT scan to check the status of the disease.

At any time the doctor thinks it is needed:

- You may have an EKG.

- Urine may be collected for routine tests.

Follow-Up:

About 30 days after your last dose of study drugs:

- You will have a physical exam.

- Blood (about 3 teaspoons) will be drawn for routine tests.

About 60 days after your last dose of study drug(s), blood (about 2 teaspoons) will be drawn
for routine tests.

About 90 days after your last dose of study drug(s), blood (about 5 teaspoons) will be drawn
for routine, antibody, biomarker, and PK testing. Antibodies are created by the immune system
and may attack foreign cells or substances, such as the study drugs.

If you cannot or do not want to come back to the clinic for these follow-up visits the study
staff will call you and you will be asked how you are feeling and about any side effects you
may have. This call should take about 5 minutes.

Long-Term Follow-up:

Starting at about Month 4 after your last dose of study drugs and every 3 months after that
until the study ends, the study staff will either call you or you will come in for a clinic
visit and you will be asked how you are feeling and about any side effects you may have. If
you are called, the call should take about 5 minutes.

If you have severe side effects, you may return to the clinic more often so the study doctor
can check on your health.

About Month 6 after your last dose of study drugs, blood (about 2 teaspoons) will be drawn
for antibody testing.

At Month 12 and then every 6 months after that, blood (about 1 teaspoon) will be drawn for
routine tests.

You will continue to have MRI/CT scans every 8-12 weeks, depending on the status of the
disease. If the disease gets worse, these scans will stop.

Inclusion Criteria:

1. Written informed consent.

2. Age >/= 18 years at time of study entry.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Life expectancy of >/= 52 weeks.

5. Adequate normal organ and marrow function as defined below: 1) Hemoglobin >/= 11.0
g/dL. 2) Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L (> 1500 per mm^3). 3)
Platelet count >/= 100 x 10^9/L (>100,000 per mm^3). 4) Serum bilirubin institutional upper limit of normal (ULN). This will not apply to subjects with
confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will
be allowed only in consultation with their physician. 5) AST (SGOT/ALT (SGPT) x institutional upper limit of normal.

6. Inclusion Criteria 5) continued: 6) Serum creatinine CL>40 mL/min by the
Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for
determination of creatinine clearance: Males: Creatinine (mL/min) Clearance (CL) =
Weight (kg) x (140 minus Age) / 72 x serum creatinine (mg/dL)

7. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

8. Consent to MD Anderson laboratory protocol PA13-0291 and LAB02-152

9. Willing to have peripheral blood mononuclear cells and bone marrow biopsies to be
collected prior to receiving the first dose of durvalumab and tremelimumab, after
2-doses and 4-doses of durvalumab and tremelimumab, after 2nd treatment administration
and 4th treatment administration.

10. Histologically or cytologically confirmed adenocarcinoma of the prostate.

11. Evidence of metastatic disease to the bone seen on most recent bone scan, computed
tomography (CT) scan and/or magnetic resonance imaging (MRI).

12. Asymptomatic or minimally symptomatic patients (do not require narcotics for prostate
cancer-related pain).

13. Tumor progression while on hormone therapy with castrate levels serum testosterone
( the Prostate Cancer Working Group 3 (PCWG3). Castrate levels of testosterone must be
maintained by surgical or medical means throughout the conduct of the study.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site), previous enrollment in the present study.

2. Participation in another clinical study with an investigational product during the
last 4 weeks.

3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an
anti-CTLA4, including tremelimumab.

4. History of another primary malignancy except for: 1) Malignancy treated with curative
intent and with no known active disease >/=5 years before the first dose of study drug
and of low potential risk for recurrence. 2) Adequately treated non-melanoma skin
cancer or lentigo maligna without evidence of disease. 3) Adequately treated carcinoma
in situ without evidence of disease (eg, superficial bladder cancer).

5. Evidence of visceral metastasis to the liver.

6. Prior use of taxane-based chemotherapy for treatment of castrate resistant prostate
cancer.

7. Receipt of the last dose of anti-cancer therapy (immunotherapy, endocrine therapy [eg,
abiraterone acetate, enzalutamide], targeted therapy, biologic therapy, tumor
embolization, monoclonal antibodies, other investigational agent) the first dose of study drug. (With the exception of those treatments described in
exclusion #3)

8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of durvalumab or tremelimumab. Note: Local surgery of isolated lesions for
palliative intent is acceptable.

9. QT interval corrected for heart rate using Fridericia's formula (QTcF) >/=470 ms. Any
clinically significant abnormalities detected, require triplicate electrocardiogram
(ECG) results and a mean QT interval corrected for heart rate using Fridericia's
formula (QTcF) >/=470 ms calculated from 3 ECGs.

10. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab or tremelimumab, with the exceptions of: intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid or steroids as
pre-medication for hypersensitivity reactions (eg CT scan premedication)

11. Any unresolved toxicity (CTCAE Grade >/=2) from previous anti-cancer therapy. Subjects
with irreversible toxicity that is not reasonably expected to be exacerbated by the
investigational product may be included (e.g., hearing loss, peripherally neuropathy).

12. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or
Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion: 1) Patients with vitiligo or alopecia; 2) Patients with hypothyroidism (eg,
following Hashimoto syndrome) stable on hormone replacement; 3) Any chronic skin
condition that does not require systemic therapy; 4) Patients without active disease
in the last 5 years may be included but only after consultation with the study
physician; 5) Patients with celiac disease controlled by diet alone.Subjects with
history of diverticulitis may be included only after consultation and approval of the
study physician.

13. History of primary immunodeficiency.

14. History of allogeneic organ transplant.

15. History of hypersensitivity to the combination of durvalumab and tremelimumab.

16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent.

17. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS). Known history of positive test for
hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for
hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test
indicating acute or chronic infection.

18. History of leptomeningeal carcinomatosis.

19. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab or tremelimumab.

20. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.

21. Brain metastases or spinal cord compression unless asymptomatic or treated and stable
off steroids and anti-convulsants for at least 28 days prior to study treatment start.
Patients with suspected brain metastases at Screening should have a CT/MRI of the
brain prior to study entry.

22. Subjects with uncontrolled seizures.

23. Male patients of reproductive potential who are not willing to employ effective birth
control from screening to 180 days after the last dose of durvalumab + tremelimumab
combination therapy or 90 days after the last dose of durvalumab monotherapy,
whichever is the longer time period.