Pilot Study of SBRT and CDX-1127 in Prostate Cancer

This pilot study will be conducted in subjects with metastatic prostate cancer in order to
define whether inclusion of immune regulation agents such as CDX-1127 augments immune
responses to SBRT-treated primary tumors or metastases, and whether inclusion of CDX-1127 in
the treatment regimen results in immune responses in untreated metastases.

MAIN INCLUSION CRITERIA

Males, Age ≥ 18 years.

Participants must have histologically-proven prostrate adenocarcinoma that is
castrate-resistant. Progressive disease is defined by one or more of the following:

- A rise in PSA on two successive determinations at least one week apart and PSA level
≥2ng/ml.

- Soft-tissue progression defined by RECIST 1.1.

- Bone disease progression defined by PCWG2 with two or more new lesions on bone scan.

Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]).

Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for
at least 3 months prior to drug initiation. Patients on LHRH agonists/antagonists must
remain on these agents for the duration of the study.

Clinical metastases must be present and confirmed on imaging studies.

Participants for whom radiation therapy is recommended for the prostate gland (or prostate
bed nodule) and/or bone or soft tissue metastases.

SBRT may be administered to 1-4 sites and the treatment sites can include prostate gland
(or prostate bed nodule for post-prostatectomy patients), bone metastases, and soft tissue
metastases. Participants must have at least one site of disease that will be both
irradiated with SBRT and biopsied to evaluate immunological outcomes.

ECOG performance status 0-2.

Adequate hepatic and renal function.

MAIN EXCLUSION CRITERIA

Prior malignancies, that will affect the completion and interpretation of the study.

Patients with active CNS metastases from prostate cancer.

Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other
experimental therapy, or who have received this therapy within the preceding 4 weeks.
Patients who are currently receiving nitrosoureas or who have received this therapy within
the preceding 6 weeks are excluded.

Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other
experimental therapy, or who have received this therapy within the preceding 4 weeks.

Major surgery within 4 weeks prior to the start of study treatment.

Patients who are receiving or have previously been treated CDX-1127.

HIV positivity

Evidence of active Hepatitis B virus or Hepatitis C virus.

Patients receiving the following medications at study entry or within the preceding 4 weeks
(or longer, if otherwise specified) are excluded:

1. Checkpoint inhibitors (within the preceding12 weeks)

2. Allergy desensitization injections

3. Systemic corticosteroids of more than 10 mg per day of prednisone (or equivalent),
administered parenterally or orally, except for physiologic replacement. Inhaled
steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical
corticosteroids are acceptable, including steroids with very low solubility
administered nasally for local effects only (e.g. Nasonex®)

4. Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).

5. Interferon or interleukin therapy

6. Other Agents with putative immunomodulating activity. (e.g. sipuleucel-T (Provenge ®))

Other investigational drugs or investigational therapy if the patient is currently taking
those drugs/therapy, or if they have received the drugs/therapy within 4 weeks prior to the
start of study treatment.

Participants must not have had prior autoimmune disorders requiring cytotoxic or
immunosuppressive therapy, or autoimmune disorders with visceral involvement.

Significant cardiovascular disease.

Active bleeding disorders or evidence of chronic or acute disseminated intravascular
coagulation (DIC).

Concomitant therapeutic anticoagulation (i.e., warfarin) for reasons other than venous
catheter patency.