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

PURPOSE: Catumaxomab is a trifunctional monoclonal antibody with binding sites directed to human EpCAM and the human T cell antigen CD3 (anti-EpCAM x 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<or=2.5 ULN. Escalating doses of catumaxomab were administered over 8 h as a continuous intravenous infusion. Dose escalation started at 2 microg and was increased to 7.5 microg. 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 microg catumaxomab) and V (40 mg dexamethasone followed by 7.5 microg 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 microg 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.