Phase II clinical trial to evaluate the safety of repeated cycles of intraperitoneal catumaxomab for the treatment of malignant ascites (SECIMAS).

Abstract

TPS155 Background: The trifunctional anti-EpCAM/anti-CD3 antibody catumaxomab has been recently approved in the EU for i.p. treatment of malignant ascites as one cycle of 4 i.p. applications within 11 days. As a growing number of clinicians are gathering experience with this antibody, the question arised, if a second treatment cycle could be feasible and effective for patients who did profit from the first cycle but eventually presented back with recurrent malignant ascites. Up to this point it remained unclear if human-anti-mouse-antibody (HAMA) would interfere with the efficiency of a second cycle, due to interception of the antibody. In a case of a patient with heavily pretreated breast cancer the patient was retreated with 4 i.p. applications of catumaxomab (10–20–50–150 μ g), which was well tolerated. HAMA-values were measured in the patients blood and ascites at different time intervals before, during and after this second cycle of catumaxomab. During this second treatment cycle a clear reduction of tumor cells and an increase of immune active cells in ascites samples could be observed, which was corresponding to a prolonged paracentesis free interval. This treatment effect was observed despite increasing HAMA response in the patients ascites and blood (340/1,627 ng/ml before and up to 587983/783893 ng/ml after treatment in ascites/plasma). On the basis of this first experience with a second cycle of catumaxomab in a patient, an open-label, single-arm phase II study was initialized. Methods: Systematic data concerning a second cycle of catumaxomab (10-20-50-150 μ g i.p.) are collected and analyzed in this study to investigate the safety, treatment effect, quality of life, pharmacokinetic, pharmakodynamics/immune status. In this roll-over concept up to 30 patients with a paracentesis free interval of at least 60 days after first cycle of catumaxomab within the randomized phase IIIb CASIMAS study (3h infusion; with versus without corticoid premedication) are included. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech, Fresenius Biotech GmbH, TRION Pharma, TRION Research, TRION Research GmbH Fresenius Biotech, GlaxoSmithKline TRION Pharma Fresenius Biotech