ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment

PRIMARY OBJECTIVES:

I. To evaluate the safety of ONTAK infusion in patients with advanced refractory breast
cancer.

II. To evaluate the effect of ONTAK administration on peripheral blood T-regulatory cells.

SECONDARY OBJECTIVES:

I. To evaluate the incidence of IL-2R expression in tumor samples and investigate the
correlation of tumor IL-2R expression and tumor response to ONTAK therapy.

II. To evaluate levels of circulating sIL-2R before and after ONTAK therapy. III. To evaluate
the effect of ONTAK on endogenous tumor specific immunity. IV. To evaluate the potential
anti-tumor effects of ONTAK in patients with advanced refractory breast cancer.

OUTLINE:

Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to
6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Patients with advanced stage refractory breast cancer

- Progressive or relapsed disease following standard therapy

- Patients must have measurable disease that can include, but is not limited to bone;
specifically, patients must have measurable extraskeletal disease that can be
accurately measured in at least one dimension as >= 20 mm with conventional CT
techniques or >= 10 mm with spiral CT scan; measurable (bi-dimensional) chest wall
disease will also be allowed

- Patients must be at least 14 days out from last cytotoxic chemotherapy; patients on
bisphosphonates are eligible

- White blood cell count (WBC) > 3.0 THOU/ul

- ANC > 1.0 THOU/ul

- Platelets >= 100 THOU/ul

- Serum creatinine =< 2.0 mg/dL or creatinine clearance (calculated) >= 60 ml/min

- ALT/AST =< 2.0 x upper limit of normal

- Total bilirubin =< 1.5 x upper limit of normal

- Albumin >= 3.0 g/dL

- Subjects must have a Performance Status Score (ECOG Scale) =< 2

- Subjects must have recovered from major infections and/or surgical procedures and, in
the opinion of the investigator, not have a significant active concurrent medical
illness precluding protocol treatment

- Men and women of reproductive ability must agree to contraceptive use during the study
and for 1month after ONTAK treatment is discontinued

Exclusion Criteria:

- Prior treatment with ONTAK (DAB389 IL-2) or DAB486 IL-2

- Known history of hypersensitivity to diphtheria toxin or IL-2

- Active autoimmune disease

- Known history of pulmonary disease except controlled asthma

- History of or pre-existing, cardiovascular disease as defined by New York Heart
Association (NYHA) Class III-IV categorization

- Pregnant or breast-feeding women