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Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab (anti-EpCAM × anti-CD3): a phase I study

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose

Catumaxomab is a trifunctional monoclonal antibody with binding sites directed to human EpCAM and the human T cell antigen CD3 (anti-EpCAM × anti-CD3). Catumaxomab demonstrated efficacy when administered intraperitoneally in patients with EpCAM positive malignant ascites from ovarian cancer in terms of tumor cell killing and reduction of ascites generation. As EpCAM is also overexpressed in NSCLC, the present study was conducted in order to evaluate safety and tolerability of intravenous treatment with catumaxomab.

Patients and methods

UICC stage IB–IV NSCLC patients were eligible, if they had at least one prior therapy. Other inclusion criteria were: age 18–75 years, adequate bone marrow function and AST or gamma-GT ≤ 2.5 ULN. Escalating doses of catumaxomab were administered over 8 h as a continuous intravenous infusion. Dose escalation started at 2 μg and was increased to 7.5 μg. In addition various doses of dexamethasone as premedication were investigated. All patients were pretreated with antihistamines.

Results

Dose limiting toxicity (DLT) was a grade 3 and 4 elevation of ALT, AST and gamma-GT, which was observed in dose level IV (10 mg dexamethasone premedication, 5 μg catumaxomab) and V (40 mg dexamethasone followed by 7.5 μg catumaxomab). Elevated liver enzymes decreased to grade 2 within 3–7 days and were at baseline level within 14 days after infusion. The maximum tolerated dose (MTD) was defined in dose level III (40 mg of dexamethasone followed by 5 μg of catumaxomab).

Conclusions

Five micrograms of catumaxomab with a pre-medication of 40 mg dexamethasone and antihistamines can be recommended as first dose for i.v. therapy consisting of multiple catumaxomab infusions for patients with NSCLC.

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Authors and Affiliations

  1. III. Medical Clinic, Department of Pulmonary Medicine, University of Mainz, Langenbeckstr, 55101, Mainz, Germany

    Martin Sebastian, Rainer Wiewrodt & Roland Buhl

  2. Department of Thoracic Surgery, University of Freiburg, Freiburg, Germany

    Bernward Passlick

  3. Fresenius Biotech GmbH, Munich, Germany

    Hilke Friccius-Quecke

  4. TRION Research GmbH, Munich, Germany

    Michael Jäger

  5. TRION Pharma GmbH, Munich, Germany

    Horst Lindhofer

  6. Pulmonary Research Institute, Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Grosshansdorf, Germany

    Frank Kanniess

  7. Department for Haematology, Oncology and Transfusion Medicine, Charité Campus Benjamin Franklin, Berlin, Germany

    Eckhard Thiel & Alexander Schmittel

Authors
  1. Martin Sebastian
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  2. Bernward Passlick
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  3. Hilke Friccius-Quecke
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  4. Michael Jäger
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  5. Horst Lindhofer
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  6. Frank Kanniess
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  7. Rainer Wiewrodt
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  8. Eckhard Thiel
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  9. Roland Buhl
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  10. Alexander Schmittel
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Correspondence to Martin Sebastian.

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Sebastian, M., Passlick, B., Friccius-Quecke, H. et al. Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab (anti-EpCAM × anti-CD3): a phase I study. Cancer Immunol Immunother 56, 1637–1644 (2007). https://doi.org/10.1007/s00262-007-0310-7

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  • DOI: https://doi.org/10.1007/s00262-007-0310-7

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