Patient case: 45-year-old female with colon cancer; genetic feature: ERBB2 amplification

Clinical trial: Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer Progressing After Endocrine Treatment

Summary: 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.

Detailed description: 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.

Eligibility: 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

Relevance to patient case: not relevant