Phase II Study Of The Trifunctional Bispecific Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab In Patients With HER-2/Neu Overexpressing (3+ Or 2+/FISH+) Metastatic Breast Cancer Progressing After Trastuzumab Treatment

Key

Inclusion Criteria:

- Women ≥ 18 years, Negative pregnancy test at screening and life expectancy of at
least 3 months

- metastatic (stage IV) and not curable adenocarcinoma of the breast

- Measurable disease, defined as at least one lesion that is measurable in one
dimension (RECIST)

- HER-2 overexpression 3+ or 2+ FISH positive

- Patients must have received one prior therapy with trastuzumab as last treatment
before entry into the study. If trastuzumab was given as single agent treatment,
patients must have received prior chemotherapy for metastatic disease

- Trastuzumab has been discontinued before study entry

- disease had progressed during or after trastuzumab therapy

- Eastern Cooperative Oncology Group (ECOG)performance score of ≤ 2

- Adequate hematological, liver and kidney function

Key Exclusion Criteria:

- Women who are pregnant or breast feeding

- Any history or symptoms indicative of brain or central nervous system metastases

- Prior diagnosis of any malignancy not cured by surgery alone less than 5 years before
study entry (except in situ carcinoma of the cervix or adequately treated basal cell
carcinoma of the skin)

- Human anti-murine antibody positive or hypersensitivity to murine proteins and any
other component of the study drug

- Known autoimmune diseases, Human immunodeficiency virus (HIV), hepatitis B or C
infection as well as other acute or chronic infection or other concurrent
non-malignant co-morbidities that are uncontrolled

- Any concurrent chemotherapy, hormonal therapy, immunotherapy or corticoid therapy

- Concurrent antibiotic treatment

- Any concurrent investigational treatment for metastatic disease

Cardiovascular exclusion criteria:

- Unstable or uncontrolled pectorial angina

- Myocardial infarction during the last 6 months

- Valvular heart disease that requires treatment

- Cardiomyopathy (congestive, hypertrophic or restrictive)

- Acute myocarditis

- Congestive heart failure (CHF): dyspnea, clinically or radiologically diagnosed

- Left ventricular ejection fraction (LVEF)outside institution's normal range based on
echocardiography at rest

- Left ventricular diameter > 56 mm based on M-mode echocardiography at rest

- Arrhythmias that require treatment (atrioventricular block II/III degree, atrial
fibrillation, ventricular tachycardia)

- Poorly or uncontrolled hypertension, asthma, seizures, allergies, pulmonary
dysfunction