PSCA-CAR T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer

PRIMARY OBJECTIVES:

I. Define the safety and tolerability of autologous
anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes (PSCA-CAR T cells) in metastatic
castration resistant prostate cancer (mCRPC).

II. Define the recommended phase 2 dose (RP2D) of PSCA-CAR T cells in mCRPC.

SECONDARY OBJECTIVES:

I. Assess the expansion and persistence of PSCA-CAR T cells. II. Assess clinical response
based on Prostate Cancer Working Group 3 (PCWG3) criteria.

III. Assess survival outcomes (including biochemical progression free survival [PFS],
radiographic PFS and overall survival [OS]).

IV. Assess serum cytokine profiles in peripheral blood pre- and post-therapy. V. Describe the
PSCA expression level on tumor cells prior to CAR T cell infusion, and the relationship it
may have with disease response and observed toxicities.

EXPLORATORY OBJECTIVES:

I. Characterize the phenotypes and frequencies of immune cell subsets in the peripheral blood
pre- and post-therapy.

II. Enumerate and characterize tumor-infiltrating lymphocytes (TILs) pre- and post-therapy.

III. Enumerate and analyze gene expression of circulating tumor cells (CTC) pre- and
post-therapy.

IV. Analyze circulating cell-free DNA (cfDNA). V. Determine the immunogenicity of PSCA-CAR T
cells.

OUTLINE: This is a dose-escalation study.

Patients may receive lymphodepleting regimen at the discretion of the treating physician
including fludarabine intravenously (IV) on days -5 to -3 and cyclophosphamide IV on days -5
to -3 or on days -4 and/or -3. Patients then receive autologous
anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0.

After completion of study treatment, patients are followed up at day 1, every 2 days for up
to 14 days, weekly for up to 1 month, every month for up to 1 year, and then annually for up
to 15 years.

Inclusion Criteria:

- All subjects must have the ability to understand and the willingness to sign a written
informed consent

- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 or Karnofsky
performance status (KPS) performance status of 70% or greater

- Documented castration resistant prostate cancer (mCRPC) (Note: castration will be
defined by a testosterone < 50 ng/dL achieved by orchiectomy or luteinizing
hormone-releasing hormone [LHRH] agonist/antagonist therapy)

- Progression of disease manifest by one of the following means during treatment
with at least one advanced androgen targeted therapy (e.g., abiraterone or
enzalutamide)

- Rising PSA documented on 2 occasions at least 7 days apart, with absolute
increase > 2 ng/dL despite testosterone < 50

- Radiographic evidence of new metastatic foci on computed tomography (CT) or
bone scan, or soft tissue progression by Response Evaluation Criteria in
Solid Tumors (RECIST)

- Prior chemotherapy with cabazitaxel and/or docetaxel is allowed but not required. If
there has been prior chemotherapy, at least 3 months must have elapsed since
completion of therapy

- Prior radiotherapy is allowed provided it was not administered to the only evaluable
site of disease and was > 14 days prior to screening

- No known contraindications to leukapheresis, steroids or tocilizumab

- Total serum bilirubin =< 2.0 mg/dL (to be performed within 42 days prior to day 1 of
protocol therapy)

- Patients with Gilbert syndrome may be included if their total bilirubin is >= 3.0
x upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN

- Aspartate aminotransferase (AST) < 3 x ULN (to be performed within 42 days prior to
day 1 of protocol therapy)

- Alanine aminotransferase (ALT) < 3 x ULN (to be performed within 42 days prior to day
1 of protocol therapy)

- Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula (to be performed
within 42 days prior to day 1 of protocol therapy)

- If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin
(PT) =< 1.5 x ULN (to be performed within 42 days prior to day 1 of protocol therapy).
If on anticoagulant therapy: PT must be within therapeutic range of intended use of
anticoagulants

- If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x
ULN (to be performed within 42 days prior to day 1 of protocol therapy). If on
anticoagulant therapy: aPTT must be within therapeutic range of intended use of
anticoagulants

- Cardiac function (12 lead-electrocardiography [ECG]) (to be performed within 42 days
prior to day 1 of protocol therapy)

- Left ventricular ejection fraction > 40% (to be performed within 42 days prior to day
1 of protocol therapy)

- Pulmonary function tests (diffusing capacity of the lung for carbon monoxide [DLCO] of
40% of best predicted) (to be performed within 42 days prior to day 1 of protocol
therapy)

- Subjects of reproductive potential must agree to use acceptable birth control methods
throughout therapy and for 3 months after final study treatment

Exclusion Criteria:

- Taxane chemotherapy or radium223 within 3 months of study screening

- Concurrent use of systemic corticosteroids or chronic use of immunosuppressant
medications above physiologic replacement doses (prednisone =< 7.5 mg /day, or
hydrocortisone =< 20 mg /day is allowed). Recent or current use of inhaled steroids is
not exclusionary

- Subjects with clinically significant arrhythmia or arrhythmias not stable on medical
management within two weeks of screening

- Subjects with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system, including
seizure disorder

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition or other agents used in this study

- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

- History of stroke or intracranial hemorrhage within 6 months prior to screening

- History of other malignancies, except for malignancy surgically resected (or treated
with other modalities) with curative intent, basal cell carcinoma of the skin or
localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer;
malignancy treated with curative intent with no known active disease present for >= 3
years

- Uncontrolled active infection

- Active hepatitis B or hepatitis C infection

- Human immunodeficiency virus (HIV) infection

- Any other condition that would, in the investigator?s judgment, contraindicate the
subject?s participation in the clinical study due to safety concerns with clinical
study procedures

- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)