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

• ClinicalTrials.gov Identifier: NCT00452140
• Recruitment Status: Terminated
• First Posted: March 27, 2007
• Last Update Posted: May 19, 2009
• Sponsor: Neovii Biotech
• Information provided by: Neovii Biotech

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer; Advanced Breast Cancer	Biological: ertumaxomab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study for Repeated Dosing of the Trifunctional Bispecific Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab in Patients With HER-2/Neu 1+ or 2+/FISH Negative Expressing Advanced or Metastatic Breast Cancer (Stage IIIb/IV) Progressing After Endocrine Treatment
• Study Start Date: March 2007
• Actual Study Completion Date: February 2009

Arms and Interventions

Intervention Details:

• Biological: ertumaxomab
  10 µg, IV on day 0 followed by 100 µg every 7 days up to a maximum of 12 infusions.

Outcome Measures

Primary Outcome Measures :

1. Clinical efficacy measured by objective response rate (best response during the course of the study)

Secondary Outcome Measures :

1. Efficacy:
2. Clinical benefit rate
3. Duration of response
4. Time to progression (TTP)
5. Safety:
6. Incidence of adverse events (AEs)
7. Presence of human anti-murine antibodies after ertumaxomab infusion
8. Vital signs
9. Laboratory parameters

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Austria

Study site, Austria

France

Study site, France

Germany

Study sites, Germany

Italy

Study site, Italy

Spain

Barcelona, Spain

Sponsors and Collaborators

Neovii Biotech

Investigators

• Principal Investigator: José Baselga / Javier Cortes; Hospital Vall d'Hebron, Barcelona, Spain

More Information

Publications:

Kiewe P, Hasmüller S, Kahlert S, Heinrigs M, Rack B, Marmé A, Korfel A, Jäger M, Lindhofer H, Sommer H, Thiel E, Untch M. Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res. 2006 May 15;12(10):3085-91.

Zeidler R, Mysliwietz J, Csánady M, Walz A, Ziegler I, Schmitt B, Wollenberg B, Lindhofer H. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells. Br J Cancer. 2000 Jul;83(2):261-6.

Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999 Aug 1;163(3):1246-52.

Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34.

• Responsible Party: Fresenius Biotech GmbH
• ClinicalTrials.gov Identifier: NCT00452140
• Other Study ID Numbers: IV-ERT-BC-03; EudraT number: 2006-005017-36
• First Posted: March 27, 2007
• Last Update Posted: May 19, 2009
• Last Verified: May 2009

Keywords provided by Neovii Biotech:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases