Stereotactic Body Radiation and Monoclonal Antibody to OX40 (MEDI6469) in Breast Cancer Patients With Metastatic Lesions
Stereotactic Body Radiation and Monoclonal Antibody to OX40 (MEDI6469) in Breast Cancer Patients With Metastatic Lesions
This study will test the investigational antibody, MEDI6469 (anti-OX40), in combination with
 stereotactic body radiation in breast cancer patients that have liver or lung metastases and
 have received systemic therapy and have progressive disease. The investigators hypothesize
 that SBRT directed at metastatic breast cancer lesions will result in a systemic anti-tumor
 immune system response. This amplified and directed immune response could result in
 anti-tumor responses.
Patients will receive one of three different doses of SBRT depending on which cohort they are
 in. The doses are:

 Cohort 1: 15 Gy (central tumors 10 Gy); Cohort 2: 20 Gy (central tumors 15 Gy); Cohort 3: 20
 Gy x 2 (central tumors 15 Gy x 2).

 In addition, all patients will receive three doses of MEDI6469. MEDI6469 is administered at
 0.4 mg/kg IV over 60 minutes using in-line filter on Days 1, 3, and 5.
Inclusion Criteria:

 -  Histologically confirmed breast cancer with clinical evidence of stage 4 disease

 -  Measurable disease and at least one lesion in either liver or lung that is amenable to
 stereotactic body radiation

 -  One site of disease that will not receive radiation

 -  Patients with hormone receptor positive breast cancer must have received prior
 anti-hormonal therapy for metastatic disease and have progressed and patients with
 hormone receptor negative breast cancer must have received at least one prior
 chemotherapy regimen and progressed.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

 -  Women of childbearing potential must have a negative pregnancy test on the day
 treatment starts and must avoid becoming pregnant while on treatment. Men must avoid
 fathering a child while on treatment.

 -  Patients must have blood test results within pre-specified range

 -  No active bleeding

 -  No clinical coagulopathy (INR <1.5, PT <16 seconds, PTT < 38 seconds) within 28 days

 -  Anticipated lifespan greater than 12 weeks

 Exclusion Criteria:

 -  Active infection requiring systemic antibiotics.

 -  Active autoimmune disease as defined by the autoimmune disease assessment tool.

 -  Previous treatment with mouse monoclonal antibodies

 -  At least 28 days since prior chemotherapy or monoclonal antibody therapy (trastuzumab
 or bevacizumab). Patients who have been on hormonal therapy can continue on therapy at
 the discretion of the investigator. Bisphosphonate therapy is acceptable during study
 participation.

 -  Diagnosis of a solid tumor malignancy (excluding non-melanoma skin cancer) within 3
 years of enrollment.

 -  Need for chronic maintenance oral steroids.

 -  Active brain metastatic disease. Treated brain metastases with surgery, gamma-knife
 radiosurgery or radiation and stable for at least 4 weeks and off steroids are
 eligible.

 -  No metastatic site amenable to SBRT

 -  Pregnant or lactating women, as treatment involves risks to the embryo or fetus.

 -  Other medical or psychiatric conditions that in the opinion of the Principal
 Investigator would preclude safe participation in protocol.