Cancer Immunology, Immunotherapy

, Volume 56, Issue 10, pp 1637–1644 | Cite as

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

  • Martin Sebastian
  • Bernward Passlick
  • Hilke Friccius-Quecke
  • Michael Jäger
  • Horst Lindhofer
  • Frank Kanniess
  • Rainer Wiewrodt
  • Eckhard Thiel
  • Roland Buhl
  • Alexander Schmittel
Original Article

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.

Keywords

Catumaxomab Trifunctional Antibody Anti-EpCAM NSCLC Phase I 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Martin Sebastian
    • 1
  • Bernward Passlick
    • 2
  • Hilke Friccius-Quecke
    • 3
  • Michael Jäger
    • 4
  • Horst Lindhofer
    • 5
  • Frank Kanniess
    • 6
  • Rainer Wiewrodt
    • 1
  • Eckhard Thiel
    • 7
  • Roland Buhl
    • 1
  • Alexander Schmittel
    • 7
  1. 1.III. Medical Clinic, Department of Pulmonary MedicineUniversity of MainzMainzGermany
  2. 2.Department of Thoracic SurgeryUniversity of FreiburgFreiburgGermany
  3. 3.Fresenius Biotech GmbHMunichGermany
  4. 4.TRION Research GmbHMunichGermany
  5. 5.TRION Pharma GmbHMunichGermany
  6. 6.Pulmonary Research InstituteHospital Grosshansdorf, Center for Pneumology and Thoracic SurgeryGrosshansdorfGermany
  7. 7.Department for Haematology, Oncology and Transfusion MedicineCharité Campus Benjamin FranklinBerlinGermany

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