phase ii study with the trifunctional antibody ertumaxomab to treat metastatic breast cancer progressing after endocrine treatment

Conditions: Metastatic Breast Cancer; Advanced Breast Cancer

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.

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 criteria:
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

Keywords: breast cancer investigational drug drug therapy antineoplastic protocols immunotherapy metastatic breast cancer advanced breast cancer stage iii to iv breast cancer hormonal therapy refractory failure of hormonal therapy her-2/neu expressing breast cancer her-2/neu