Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers

852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24
doses) with provisions for dose escalation or reduction based on tolerability.

Inclusion Criteria:

- Adequate performance status:

- Breast - Karnofsky score > 50;

- Ovarian, endometrial or cervical - Gynecologic Oncology Group (GOG) performance
score ≤2

- If female and of childbearing potential, are willing to use adequate contraception
(hormonal, barrier method, abstinence) prior to study entry and for the duration of
study participation.

- Normal organ function within 14 days of study entry

- Diagnosis of one of the following malignancies:

- Metastatic breast cancer (BR)

- Metastatic ovarian cancer (OV)

- Metastatic endometrial cancer (EM)

- Metastatic cervical cancer (CX)

Breast Cancer Inclusion Criteria:

- Measurable metastatic disease (>1cm) in at least one site other than bone-only

- Progression on or failure to respond to at least one previous chemotherapy regimen for
metastatic disease

- Progression on prior therapy with a hormonal agent if estrogen receptor or
progesterone receptor positive, and/or with trastuzumab if HER2-neu positive. If
patient has progressed through hormone or trastuzumab therapy only, must have received
one chemotherapy regimen.

Ovarian Cancer Inclusion Criteria:

- Measurable metastatic disease as defined by Response Evaluation Criteria in Solid
Tumors (RECIST)

- Primary tumor must have been diagnosed histologically as either epithelial ovarian
cancer, fallopian tube cancer, or primary peritoneal cancer (not borderline or low
malignant potential epithelial carcinoma).

- Subjects must have failed at least two previous chemotherapy regimens. Paclitaxel must
have been a component of one or both regimens and cisplatin or carboplatin must have
been a component of one or both regimens.

Endometrial Cancer Inclusion Criteria:

- Measurable metastatic disease

- Histologically proven recurrent or persistent endometrial cancer that is not amenable
to curative treatment with surgery and/or radiation therapy AND has failed 2 previous
treatment regimens

Cervical Cancer Inclusion Criteria:

- Measurable metastatic disease

- Histologically proven recurrent or persistent squamous cell carcinoma, adenosquamous
carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment
with surgery and/or radiation therapy AND has failed 2 previous treatment regimens.

Exclusion Criteria:

- Had/have the following prior/concurrent therapy:

- Systemic corticosteroids (oral or injectable) within 7 days of first dose of 852A
(topical or inhaled steroids are allowed)

- Investigational drugs/agents within 14 days of first dose of 852A

- Immunosuppressive therapy, including cytotoxic agents within 14 days of first
dose of 852A (nitrosoureas within 30 days of first dose)

- Drugs known to induce QT interval prolongation and/or induce Torsades de pointes
unless best available drug required to treat life-threatening conditions

- Radiotherapy within 3 weeks of the first dose of 852A

- Hematopoietic cell transplantation within 4 weeks of first dose of 852A

- Evidence of active infection within 3 days of first dose of 852A

- Active fungal infection or pulmonary infiltrates (prior treated disease stable
for 2 weeks is allowable)

- Cardiac ischemia, cardiac arrhythmias or congestive heart failure uncontrolled by
medication

- History of, or clinical evidence of, a condition which, in the opinion of the
investigator, could confound the results of the study or put the subject at undue
risk

- Uncontrolled intercurrent or chronic illness

- Active autoimmune disease requiring immunosuppressive therapy within 30 days

- Active coagulation disorder not controlled with medication

- Pregnant or lactating

- Concurrent malignancy (if in remission, at least 5 years disease free) except for
localized (in-situ) disease, basal carcinomas and cutaneous squamous cell
carcinomas that have been adequately treated

- Any history of brain metastases or any other active central nervous system (CNS)
disease