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

Morten Mau-Sørensen, Christian Dittrich, Rodrigo Dienstmann, Ulrik Lassen, Wilfried Büchler, Holger Martinius, Josep Tabernero

    52 Citationer (Scopus)

    Abstract

    PURPOSE: 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.

    METHODS: 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 ≥grade 3 optimally treated non-hematological toxicity; ≥grade 3 infusion-related reactions refractory to supportive care; ≥grade 3 increase in liver enzymes and/or bilirubin not resolving to grade 2.

    RESULTS: Sixteen patients were enrolled receiving doses of 2 (n = 5), 4 (n = 3), 7 (n = 7) and 10 µg 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 ≥3 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-µg dose level was considered a DLT. The first patient at 10 µg experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study.

    CONCLUSIONS: The MTD of weekly intravenous catumaxomab was 7 µg. Major toxicities were cytokine release-related symptoms and hepatotoxicity.

    OriginalsprogEngelsk
    TidsskriftCancer Chemotherapy and Pharmacology
    Vol/bind75
    Udgave nummer5
    Sider (fra-til)1065-73
    Antal sider9
    ISSN0344-5704
    DOI
    StatusUdgivet - maj 2015

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