A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3

The aim of the study was to evaluate the safety and determine the maximum tolerated dose (MTD) of intravenous catumaxomab, a trifunctional bispecific antibody that binds to EpCAM on epithelial cancer cells and CD3 on T cells. The trial was a dose-escalation study with a 3 + 3 design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab. Key DLTs were a parts per thousand yengrade 3 optimally treated non-hematological toxicity; a parts per thousand yengrade 3 infusion-related reactions refractory to supportive care; a parts per thousand yengrade 3 increase in liver enzymes and/or bilirubin not resolving to grade 2. Sixteen patients were enrolled receiving doses of 2 (n = 5), 4 (n = 3), 7 (n = 7) and 10 A mu g catumaxomab (n = 1). The most common treatment-emergent adverse events (TEAEs) were chills (93.8 %) and pyrexia (87.5 %). The most common TEAE of grade a parts per thousand yen3 was transient dose-dependent increases in aspartate aminotransferase (56.3 %). The intensity of toxicities decreased with the number of infusions. Also, serum IL-6 increased in a dose-dependent manner and reverted to low or undetectable levels after four infusions. A reversible decrease in liver function test (prothrombin time) at the 7-A mu g dose level was considered a DLT. The first patient at 10 A mu g experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study. The MTD of weekly intravenous catumaxomab was 7 A mu g. Major toxicities were cytokine release-related symptoms and hepatotoxicity.