A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).

In the phase Ib, patients will be treated with intravesical ALT-803 in combination with BCG.
The purpose of the phase Ib portion of the study is to evaluate the safety, identify the
Maximum Tolerated Dose (MTD) of ALT-803 and determine the Recommended Dose (RD) level of
ALT-803 in combination with BCG for the phase IIb expansion.

In the phase IIb expansion, patients will be randomized to receive either intravesical
ALT-803 in combination with BCG or BCG alone.

The purpose of the phase IIb portion of the study is to compare disease response, recurrence
and survival rates, safety and quality of life between the two treatment groups.

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

- Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell
carcinoma high-grade subtype.

- Patients are eligible if the diagnostic biopsy was done within 3 months of
treatment start and a cystoscopy demonstrating no resectable disease was done
within 6 weeks of treatment start. Patients with high-grade Ta and/or T1 disease
should have complete resection before study treatment.

- Upper tract imaging within 6 months prior to study entry must not be suspicious
for upper tract malignancy.

- No history of or evidence of muscle-invasive, locally advanced, metastatic and/or
extravesical bladder cancer or presence of any other cancer.

PRIOR/CONCURRENT THERAPY:

- No prior BCG treatment or known hypersensitivity to BCG. Patients who have received
more than a single-dose post-operative treatment of mitomycin-C or gemcitabine are
excluded.

- No concurrent use of other investigational agents.

PATIENT CHARACTERISTICS:

Performance Status • ECOG 0, 1, or 2. Bone Marrow Reserve

- Absolute neutrophil count (AGC/ANC) ≥ 1,000/uL

- Platelets ≥ 100,000/uL

- Hemoglobin ≥ 8g/dL Renal Function

- Glomerular Filtration Rate (GFR) > 40mL/min or serum creatinine ≤ 1.5 x ULN Hepatic
Function

- Total bilirubin ≤ 2.0 X ULN

- AST, ALT, ALP ≤ 3.0 X ULN Cardiovascular

- No symptomatic congestive heart failure Class III or IV.

- No severe/unstable angina pectoris < 6 months.

- No myocardial infarction < 6 months. Pulmonary

- Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction.

Other

- Currently eligible for intravesical BCG therapy.

- Negative serum pregnancy test if female and of childbearing potential.

- No women who are pregnant or nursing.

- Subjects, both females and males, with reproductive potential must agree to use
effective contraceptive measures for the duration of the study.

- No known positive HIV status.

- No history or evidence of uncontrollable CNS disease.

- No psychiatric illness/social situation that would limit compliance with study
requirements.

- No other illness that in the opinion of the investigator would exclude the patient
from participating in this study.

- Must provide signed informed consent and HIPPA authorization and agree to comply with
all protocol-specified procedures and follow-up evaluations.

- No active systemic infection requiring parenteral antibiotic therapy.

- No ongoing chronic systemic steroid therapy required.

- No concurrent febrile illness, active urinary tract infection, active tuberculosis, a
history of hypotension or anaphylactic reactions.