Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer

OBJECTIVES:

Primary

- To evaluate the progression-free survival of patients with HER2-overexpressing locally
advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and
agatolimod sodium.

Secondary

- To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against
trastuzumab-coated target cells by evaluating the ability of patient immune-effector
cells to conduct ADCC and produce interferon gamma.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also
receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15,
and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.

Blood samples are collected periodically for correlative laboratory studies. Samples are
analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ
production and quantification by flow cytometry and reverse transcriptase-polymerase chain
reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer

- Locally advanced or metastatic disease

- HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified
by FISH

- Non-measurable disease allowed

- Achieved partial response, complete response, or stable disease (i.e., no disease
progression for ≥ 12 weeks) while on trastuzumab (Herceptin®) and chemotherapy,
hormonal therapy alone, or trastuzumab alone

- Last dose of trastuzumab must have been administered within the past 16 weeks

- No unstable brain metastases

- Patients with brain metastases are eligible provided they have been stable for ≥
1 month after surgery or radiotherapy/radiosurgery AND off corticosteroids and
anticonvulsants for ≥ 4 weeks

- Hormone receptor status unspecified

PATIENT CHARACTERISTICS:

- ECOG(Eastern Cooperative Oncology Group)performance status (PS) 0-2 (Karnofsky PS
70-100%)

- Absolute neutrophil count ≥ 1,500/mm³

- Hemoglobin > 8 g/dL (transfusion/epoetin alfa allowed)

- Platelet count ≥ 100,000/mm³

- Total bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if known liver metastases)

- Creatinine < 2 mg/mL

- Ejection fraction ≥ 50% by echocardiogram or MUGA

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception before, during, and for ≥ 3 months
after completion of study treatment

- No ongoing or active infection requiring oral or IV antibiotics

- No known autoimmune disorders or antibody-mediated disorders

- No known HIV positivity

- No known history of hepatitis B or C (active and/or previously treated)

- No other malignancies within the past 5 years except nonmelanoma skin cancer or
cervical cancer in situ

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to study drugs

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 12 weeks since prior chloroquine

- More than 4 weeks since prior growth factors

- More than 4 weeks since prior systemic corticosteroids

- More than 4 weeks since prior chemotherapy, radiotherapy, or monoclonal antibody
therapy (except trastuzumab)

- No prior agatolimod sodium

- No prior allogeneic stem cell transplantation

- No prior continuous treatment with single-agent trastuzumab for > 6 months

- No more than 3 prior chemotherapy regimens for metastatic breast cancer

- Any number of prior hormonal therapies allowed

- No other concurrent investigational agents or monoclonal antibodies

- No other concurrent anticancer agents or therapies

- Concurrent bisphosphonates for skeletal metastasis allowed