Dendreon Lymph Node Biopsy in Metastatic Castrate-Resistant Prostate Cancer

This is a pilot study of mCRPC patients planning to undergo therapy with sipuleucel-T
immunotherapy. Consenting patients will be randomized 3:1 between immediate sipuleucel-T
immunotherapy followed by lymph node biopsy (the post-treatment experimental group) or
immediate lymph node biopsy followed by sipuleucel-T immunotherapy (the pre-treatment control
group). Peripheral blood will be collected before, during, and after treatment with
sipuleucel-T and evaluated for evidence of sipuleucel-T induced immune activation. Lymph
nodes collected at biopsy will also be evaluated for evidence of sipuleucel-T induced immune
activation. Patients will be followed for 3 months for safety and 6 months for disease
progression.

Inclusion Criteria:

1. Age ≥ 18 years

2. ECOG performance status 0 or 1

3. Life expectancy of ≥ 6 months

4. Minimally-symptomatic or asymptomatic, castrate-resistant metastatic prostate cancer,
as evidenced by all of the following:

1. Histologically-confirmed diagnosis of adenocarcinoma of the prostate

2. Evidence of adequate androgen deprivation, as evidence by one of the following:

- Bilateral orchiectomy

- Ongoing LHRH agonist (e.g. leuprolide, goserelin) and serum testosterone <50
ng/dl

- Ongoing LHRH antagonist (e.g. degarelix) and serum testosterone <50 ng/dl

3. Evidence of prostate cancer resistance to castration, as evidenced by one of the
following:

- 2 consecutive PSA levels that are ≥ 50% above the PSA nadir achieved on ADT
and obtained at least 1 week apart

- CT or MRI based evidence of disease progression (soft tissue or nodal)
according to PCWG2 criteria or RECIST 1.1 criteria, or at least 1 new bone
scan lesion as compared to the most immediate prior radiologic studies.

4. Presence of non-visceral metastases on imaging

5. Absence of major symptoms directly attributable to prostate cancer, with the
following permissible exceptions:

- Ureteral obstruction secondary to pelvic or retroperitoneal lymphadenopathy

- Bladder outlet obstruction secondary to locally recurrent prostate cancer

5. Radiographic evidence of lymphadenopathy, defined as a lymph node greater than 1 cm in
diameter on axial imaging (CT or MRI or PET/CT)

6. Adequate laboratory parameters

7. A minimum of 4 weeks from any major surgery prior to registration. Coincident standard
of care surgery with the research biopsy is permitted during the study.

Exclusion Criteria:

1. Prior treatment with sipuleucel-T

2. Allergy to any component of sipuleucel-T

3. Inability to undergo leukapheresis

4. History of neuroendocrine variants of prostate cancer, including small cell carcinoma
of the prostate

5. Extensive prior surgery/radiation present that would render the biopsy highly complex
and the risk of intraoperative injury high

6. Any chronic medical condition requiring daily corticosteroids or other
immunosuppressants

7. Solid organ transplantation requiring immunosuppression

8. Visceral (e.g. lung, liver) metastases

9. Known brain metastases

10. History of spinal cord compression

11. Untreated/unstabilized pathologic long bone fractures

12. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of
recurrence within 24 months

13. Administration of any investigational therapeutic within 30 days of registration

14. Any condition which, in the opinion of the investigator, would preclude participation
in this trial