Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion

Antoni Ribas, Jason Chesney, Michael Gordon, Amy Abernethy, Theodore Logan, David Lawson, Bartosz Chmielowski, John Glaspy, Karl Lewis, Bo Huang, Erjian Wang, Poe-Hirr Hsyu, Jesus Gomez-Navarro, Diana Gerhardt, Margaret Marshall, Rene Gonzalez

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    30 Citations (Scopus)

    Abstract

    Background: CTLA4 blocking monoclonal antibodies provide a low frequency but durable tumor responses in patients with metastatic melanoma, which led to the regulatory approval of ipilimumab based on two randomized clinical trials with overall survival advantage. The similarly fully human anti-CTLA4 antibody tremelimumab had been developed in the clinic at a fixed rate infusion, resulting in very prolonged infusion times. A new formulation of tremelimumab allowed testing a shorter infusion time.Methods: A phase 1 multi-center study to establish the safety and tolerability of administering tremelimumab as a 1-hour infusion to patients with metastatic melanoma. Secondary endpoints included pharmacokinetic and clinical effects of tremelimumab.Results: No grade 3 or greater infusion-related adverse events or other adverse events preventing the administration of the full tremelimumab dose were noted in 44 treated patients. The overall side effect profile was consistent with prior experiences with anti-CTLA4 antibodies. Objective tumor responses were noted in 11% of evaluable patients with metastatic melanoma, which is also consistent with the prior experience with CTLA4 antagonistic antibodies.Conclusions: This study did not identify any safety concerns when tremelimumab was administered as a 1-hour infusion. These data support further clinical testing of the 1-hour infusion of tremelimumab. (Clinical trial registration number NCT00585000).

    Original languageEnglish
    Article number236
    Pages (from-to)236
    Number of pages6
    JournalJournal of Translational Medicine
    Volume10
    Issue number1
    DOIs
    Publication statusPublished - 2012

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    Ribas, A., Chesney, J., Gordon, M., Abernethy, A., Logan, T., Lawson, D., Chmielowski, B., Glaspy, J., Lewis, K., Huang, B., Wang, E., Hsyu, P-H., Gomez-Navarro, J., Gerhardt, D., Marshall, M., & Gonzalez, R. (2012). Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion. Journal of Translational Medicine, 10(1), 236. [236]. https://doi.org/10.1186/1479-5876-10-236