Treatment of malignant pleural effusion with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3): Results of a phase I/II study

Abstract

2548 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III. Thus the antibody induces tumor specific cell mediated cytotoxicity in vitro and in vivo. Its intraperitoneal administration has demonstrated safety and led to efficient tumor cell killing and reduction of malignant ascites in ovarian cancer patients (pts.). The present study was conducted to evaluate safety, tolerability and preliminary efficacy of catumaxomab administered intrapleurally (i.pl.) into pts. with EpCAM+ malignant pleural effusion. Methods: This phase I/II trial was a multi-center uncontrolled, dose-escalating study. Pts. (ECOG ≤3) with recurrent malignant pleural effusion containing EpCAM+ tumor cells were included. Three escalating doses from 5–200 μg catumaxomab were administered i.pl. Primary objectives were toxicity and definition of the maximum tolerated dose (MTD). In addition, preliminary data on efficacy (reduction of pleural fluid and tumor cell killing) were generated. Results: 13/24 pts. received 3 infusions as planned. Reasons for early termination of infusions were 3 deteriorations of performance status, 2 exanthemas, 2 dyspnoea, 2 others. The dose regimen of 20–50–100 μg catumaxomab was defined as MTD. Most frequent drug related AEs were symptoms of cytokine release syndrome. 32 SAEs were reported in 18 pts., 4 SAEs were possibly drug related (1 death due to pleural empyema, 1 pneumonia, 1 erythema, 1 increase of liver enzymes). 8/9 deaths were not drug related but due to underlying disease. Induction of human-anti-mouse (HAMA) or human-anti-rat (HARA) antibodies after treatment was found in 8/11 pts. 8/13 fully treated pts. were defined as responders (1 complete, 4 partial, 3 NA) showing reduction of effusion and of drainage necessity. 5/13 were non-responders. A reduction of tumor cells up to log 5 was seen in 10/13 pts. Conclusions: 20–50–100 μg of catumaxomab can safely be administered i. pl. This regimen will further be investigated in a randomized phase II trial comparing catumaxomab to talcum-based pleurodesis. [Table: see text]