A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) Followed by Indoximod or Placebo in the Treatment of Patients With Asymptomatic or Minimally Symptomatic Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria:

- Histologically documented adenocarcinoma of the prostate with metastatic disease as
evidenced by soft tissue and/or bony metastases on baseline computed tomography (CT)
scan of the abdomen and pelvis and/or bone scan

- Castration-resistant based on a current or historical evidence of disease progression
despite surgical or medical castration as demonstrated by one or more of the
following:

- PSA progression (defined as two consecutive prostate specific antigen (PSA)
measurements at least 14 days apart ≥ 2.0 ng/ml and ≥ 50% above the minimum PSA
during castration therapy or above pre-treatment value if no response)

- progression of measurable disease based on Response Evaluation Criteria In Solid
Tumors (RECIST) criteria (≥ 50% increase in the sum of the cross products of all
measurable lesions or the development of any new lesions

- progression of non-measureable disease

- Serum PSA ≥ 2.0 ng/ml at study enrollment

- Castration levels of testosterone defined as ≤ 30 ng/dL at study enrollment. Must be
at least 3 months from surgical castration or must have received medical castration
therapy for at least 3 months and be receiving such therapy at the time of confirmed
disease progression

- Asymptomatic or minimally symptomatic disease as demonstrated by Eastern Cooperative
Oncology Group (ECOG) Performance Status 0 or 1 and no need for opiate pain
medications to control pain/symptoms

- Age 18 years and old

- Adequate bone marrow, renal and hepatic function within 14 days of study enrollment
defined as:

- Bone marrow: WBC > 3,000/uL; absolute neutrophil count > 1,500/uL; platelets >
100,000/uL

- Renal: creatinine within institutional upper limit of normal (ULN) OR creatinine
clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above ULN

- Hepatic: total bilirubin < 1.5 X institutional ULN; aspartate aminotransferase
(AST ((SGOT)) and alanine aminotransferase (ALT((SGPT)) < 2.5 X institutional
ULN

Exclusion Criteria:

- Chronic steroid dependence (should stop all steroid supplementation 4 weeks prior to
enrollment)

- Human immunodeficiency virus (HIV)-positive patients and those with other
acquired/inherited immunodeficiency

- History of gastrointestinal disease causing malabsorption or obstruction such as, but
not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial
overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions,
achalasia, bowel obstruction, or extensive small bowel resection

- Inability to take medications by mouth

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition

- Active autoimmune disease, chronic inflammatory condition, conditions requiring
concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent
asthma requiring only occasional beta-agonist inhaler use or mild localized eczema
will not be excluded.

- Previous allo-transplant of any kind

- History of prior treatment with anti-CTLA4 blocking antibody