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

2540 Background: Catumaxomab is a trifunctional monoclonal antibody with binding specificities to human EpCAM, human CD3 and Fc gamma receptor I/III-positive accessory cells leading to induction of cell mediated, tumor specific cytotoxicity. As EpCAM is overexpressed in NSCLC patients (pts.) the present study was conducted in order to evaluate safety and tolerability of intravenous (i.v.) treatment with catumaxomab. Methods: Patients with NSCLC (UICC stage IB - IV) with at least one prior therapy were included into this trial. Escalating doses of 2–7,5 μg catumaxomab were given as a single i.v. infusion. Various doses of dexamethasone premedication (10 and 40 mg) were investigated at five different dose levels (level: catumaxomab (μg)/dexamethasone (mg)/number of pts. treated: I: 2/40/3, II: 2/0/1, III: 5/40/4, IV: 5/10/5, V: 7,5/40/2, respectively). Primary objectives were toxicity and definition of the maximum tolerated dose (MTD). In addition, time to progression (TTP) and survival were evaluated. Results: 24 pts. were included into this trial; 15 pts. were evaluable for safety analysis, 13 pts. for follow up. 13/15 pts. experienced a total of 68 AEs, of which 55 were reported as drug related and 9 defined as critical AEs. The majority (77%) of AEs were mild (CTC grade 1 and 2), 19% were grade 3 and 4% grade 4. 73% of the AEs were elevation of liver enzymes (gamma-GT, AST and ALT). Other toxicities were increase of blood ALP, dizziness, lymphopenia and pyrexia. Dose limiting toxicity (DLT) was a transient grade 3 and 4 elevation of ALT, AST and gamma-GT, observed at dose levels IV and V. Maximum tolerated dose (MTD) was defined at dose level III. Remarkably, follow up data showed 4/4 pts. stage IIIB and 1/4 pts. stage IV still alive at 26–28 months after catumaxomab treatment. Conclusion: 5 μg of catumaxomab can safely be administered intravenously with 40 mg dexamethasone as premedication. Based on the current results we recommend this regimen as first dose in a future study consisting of multiple catumaxomab infusions in pts. with locally advanced NSCLC. [Table: see text]