Ph Ib/IIa Study of Cabazitaxel Plus Bavituximab in Castration-resistant Prostate Cancer

Cabazitaxel will be administered IV on day 1 of each 21-day treatment cycle. Bavituximab (3
mg/kg) will be administered as an intravenous (IV) infusion on a weekly basis (Cycle 1 Day 2,
all other cycles Day 1; day 8, day 15). Patients will receive cabazitaxel (day 1) plus
bavituximab weekly of each 21-day cycle for up to 8 cycles.

Up to 31 patients will be enrolled to ensure 28 evaluable subjects. The accrual period is
expected to be between 12 to 18 months (1-1.5 years).

Subjects will remain on the treatment phase of the study until any of the following events
occur:

- Disease progression as evidenced by an increase in the prostate-specific antigen (PSA)
level, worsening of pain, or disease progression by Response Evaluation Criteria in
Solid Tumors (RECIST)

- Completion of 8 cycles of cabazitaxel-bavituximab therapy (day 169)

- Development of toxicity that, in the investigator's judgment, precludes further study
participation

- Significant protocol violations or noncompliance on the part of the patient or
investigator

- The investigator's judgment that discontinuation is in the patient's best interest

- Initiation of alternative antineoplastic treatments.

- Refusal of the patient to continue treatment or follow-up

- Loss to follow-up

After completion of the treatment phase, subjects will remain on the followup phase of the
study until any of the following events occur:

- Refusal of the patient to continue treatment or follow-up

- Loss to follow-up

- Death

- The investigator's judgment that discontinuation is in the patient's best interest

Inclusion Criteria:

- Written informed consent has been obtained.

- Adults 18 years of age or older with a life expectancy of at least 3 months.

- Histologically confirmed castration-resistant prostate cancer (CRPC). Patient must
have demonstrated a rising PSA level above the androgen-deprivation therapy (ADT)
nadir, on at least two determinations four weeks or more apart. ADT is defined as
treatment with a Luteinizing-hormone-releasing hormone (LHRH) agonist or orchiectomy.

- Treatment with only one prior chemotherapy regimen, which must contain docetaxel as a
single agent or in combination with other agents. Patients may be intolerant of, or
resistant to, the cytotoxic drug combination.

- Patients on ADT must be willing to continue ADT for the duration of their
participation in this protocol. ADT cannot be initiated, and ADT dose/agents may not
be changed during the study.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

- Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1,500 cells/μL;
hemoglobin ≥ 8 g/dL, platelets ≥ 100,000/μL).

- Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine
clearance ≥ 60 mL/min).

- Adequate hepatic function (bilirubin ≤ 1.0 x upper limit of normal [ULN], alanine
aminotransferase [ALT] ≤ 1.5 x ULN, aspartate aminotransferase [AST] ≤ 1.5 x ULN).

- Prothrombin time (PT) / international normalized ratio (INR) ≤ 1.5 × ULN.

- Activated partial thromboplastin (aPTT) time ≤ 1.5 × ULN.

- Prostate-specific antigen (PSA) level of at least 2 ng/mL.

- New York Heart Association classification I or II.

- All patients of reproductive potential must agree to use an approved form of
contraception (as determined by the investigator).

Exclusion Criteria:

- Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand disease or
hemophilia).

- Any history of thromboembolic events (e.g., deep vein thrombosis or pulmonary
thromboembolism); central venous catheter-related thrombosis > 6 months before
Screening is allowed.

- Ongoing therapy with oral or parenteral anticoagulants; patients on low-dose
anticoagulants to maintain patency of central venous catheters are eligible.

- Grade 2 or higher peripheral neuropathy (e.g., numbness, tingling, and/or pain in
distal extremities).

- Radiotherapy (teletherapy or brachytherapy) , chemotherapy or estrogen agonist within
28 days before Study Day 1.

- Systemic radiotherapy (Sm-153, Sr-89) within 56 days before study day 1.

- Symptomatic or clinically active brain metastases.

- Major surgery within 28 days of Study Day 1.

- Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease).

- Any history of cerebrovascular accident, or transient ischemic attack at any time, or
history of symptomatic coronary artery disease < 6 months before screening.

- A history of any condition requiring anti-platelet therapy (eg, phosphodiesterase
inhibitors, adenosine diphosphate receptor antagonists), with the exception of general
cardiovascular prophylaxis with aspirin (≤ 325 mg/day).

- Serious non-healing wound (including wound healing by secondary intention, ulcer, or
bone fracture).

- Known chronic infection with human immunodeficiency virus (HIV) or viral hepatitis.

- Contraindication to intravenous (IV) contrast media.