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The purpose of the study is to demonstrate clinical efficacy of the investigational trifunctional bispecific antibody ertumaxomab for treatment of patients with HER-2/neu 1+ or 2+ (FISH-) expressing advanced or metastatic breast cancer (stage III b/IV) which has progressed after endocrine therapy.

Ertumaxomab is a trifunctional bispecific antibody targeting Her-2/neu and CD3 on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages, dendritic cells [DCs] and natural killer [NK] cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these immune cells, which can trigger a complex anti-tumor immune response.

An open-label, non-randomized, uncontrolled, one-stage, phase II study evaluating the efficacy and safety of the investigational trifunctional bispecific antibody ertumaxomab (anti-Her-2/neu x anti-CD3) for the treatment of hormone therapy refractory advanced or metastatic breast cancer tumours (stage IIIb or IV) which are known to express HER-2/neu (1+ or 2+/FISH negative).Ertumaxomab will be administered at 7 day intervals by constant rate 3 hour intravenous (i.v.) infusions according to the following sequential dose schedule: 10 µg (day 0) and thereafter 100 µg flat doses once every 7 days (± 1 day) for a maximum of up to 12 weeks or until disease progression or any other unacceptable toxicity.

Inclusion Criteria:

• Signed and dated informed consent form
• Women ≥ 18 years, negative pregnancy test at screening life expectancy of at least 6 months
• Locally advanced (stage IIIb) or 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/neu expression 1+ or 2+ / FISH negative
• Estrogen Receptors (ERs) and/or Progesterone Receptors (PRs) positive
• Prior adequate endocrine therapy for advanced or metastatic disease
• Disease progression during or after endocrine therapy
• No prior treatment with mouse or rat antibodies
• ECOG performance score of ≤ 1
• Adequate hematological, liver and kidney function

Exclusion Criteria:

• Women who are pregnant or breast-feeding

• Known HIV infection or Presence of autoimmune disease or other Concurrent non-malignant co-morbidities that are uncontrolled

• History or symptoms indicative of brain or CNS 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)

• Documented acute or chronic infection requiring antibiotic treatment

• Any concurrent chemo-, hormonal, immuno- or corticoid therapy

• Any prior chemotherapy for advanced or metastatic disease

• Any concurrent investigational treatment for advanced or metastatic disease

• History of relevant cardiovascular disease as follows:

  • Left ventricular ejection fraction (LVEF) below the institution's lower limit of normal, based on echocardiography (ECG) at rest
  • Uncontrolled or symptomatic congestive heart failure (New York Heart Association (NYHA) > 2
  • Uncontrolled or symptomatic arrhythmia and/or angina pectoris
  • Myocardial infarction during the last 2 years