Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer

This is a single-center, single arm, open-label phase II study evaluating the safety,
anti-tumor effect, and immunogenicity of neoadjuvant MGA271 given prior to radical
prostatectomy in men with intermediate and high-risk localized prostate cancer. Eligible
patients will receive MGA271 at a dose of 15mg/kg IV given weekly for 6 doses beginning 50
days prior to radical prostatectomy. 14 days after the last dose of MGA271, prostate glands
will be harvested at the time of radical prostatectomy, and prostate tissue will be examined
for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and
90 days after surgery. Patients will then be followed by their urologists according to
standard institutional practices, but will require PSA evaluations every 3 (±1) months during
year 1 and every 6 (±2) months during years 2-3.

In Amendment 1, the study was expended to enroll an additional 16 patients for a total of 32
patients to continue evaluating safety and better estimate the clinical benefit of
Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) at 12 months following radical
prostatectomy.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0,
M0) without involvement of lymph nodes, bone, or visceral organs

- Initial prostate biopsy is available for central pathologic review, and is confirmed
to show at least 2 positive cores and a Gleason sum of ≥7

- Radical prostatectomy has been scheduled at Johns Hopkins Hospital

- Age ≥18 years

- ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)

- Adequate bone marrow, hepatic, and renal function:

- WBC >3,000 cells/mm3

- ANC >1,500 cells/mm3

- Hemoglobin >9.0 g/dL

- Platelet count >100,000 cells/mm3

- Serum creatinine <1.5 × upper limit of normal (ULN)

- Serum bilirubin <1.5 × ULN

- ALT <3 × ULN

- AST <3 × ULN

- Alkaline phosphatase <3 × ULN

- The etiology of abnormal bilirubin and transaminase levels should be evaluated prior
to study entry.

- Willingness to provide written informed consent and HIPAA authorization for the
release of personal health information, and the ability to comply with the study
requirements (note: HIPAA authorization will be included in the informed consent)

- Willingness to use barrier contraception from the time of first dose of MGA271 until
the time of prostatectomy.

Exclusion Criteria:

- Presence of known lymph node involvement or distant metastases

- Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma,
small cell, and neuroendocrine tumors

- Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for
prostate cancer

- Prior immunotherapy/vaccine therapy for prostate cancer

- Prior use of experimental agents for prostate cancer

- Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors

- Current use of systemic corticosteroids or use of systemic corticosteroids within 4
weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted as are
other non-systemic steroids such as topical corticosteroids)

- History or presence of autoimmune disease requiring systemic immunosuppression
(including but not limited to: inflammatory bowel disease, systemic lupus
erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis,
hemolytic anemia, Sjögren syndrome, and sarcoidosis)

- History of malignancy within the last 3 years, with the exception of non-melanoma skin
cancers and superficial bladder cancer

- Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or
psychiatric illnesses that would make the patient a poor study candidate

- Known prior or current history of HIV and/or hepatitis B/C