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

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

Research output: Contribution to journalArticle

29 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
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
StatePublished - Nov 21 2012

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Pharmacokinetics
Anti-Idiotypic Antibodies
Safety
Antibodies
Melanoma
Tumors
Blocking Antibodies
Testing
tremelimumab
Neoplasms
Randomized Controlled Trials
Monoclonal Antibodies
Clinical Trials
Survival

Keywords

  • CTLA4
  • Melanoma
  • Tremelimumab

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion. / Ribas, Antoni; Chesney, Jason A.; Gordon, Michael S.; Abernethy, Amy P.; Logan, Theodore; Lawson, David H.; Chmielowksi, Bartosz; Glaspy, John A.; Lewis, Karl; Huang, Bo; Wang, Erjian; Hsyu, Poe Hirr; Gomez-Navarro, Jesus; Gerhardt, Diana; Marshall, Margaret A.; Gonzalez, Rene.

In: Journal of Translational Medicine, Vol. 10, No. 1, 236, 21.11.2012.

Research output: Contribution to journalArticle

Ribas, A, Chesney, JA, Gordon, MS, Abernethy, AP, Logan, T, Lawson, DH, Chmielowksi, B, Glaspy, JA, Lewis, K, Huang, B, Wang, E, Hsyu, PH, Gomez-Navarro, J, Gerhardt, D, Marshall, MA & Gonzalez, R 2012, 'Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion', Journal of Translational Medicine, vol. 10, no. 1, 236. https://doi.org/10.1186/1479-5876-10-236
Ribas, Antoni ; Chesney, Jason A. ; Gordon, Michael S. ; Abernethy, Amy P. ; Logan, Theodore ; Lawson, David H. ; Chmielowksi, Bartosz ; Glaspy, John A. ; Lewis, Karl ; Huang, Bo ; Wang, Erjian ; Hsyu, Poe Hirr ; Gomez-Navarro, Jesus ; Gerhardt, Diana ; Marshall, Margaret A. ; Gonzalez, Rene. / Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion. In: Journal of Translational Medicine. 2012 ; Vol. 10, No. 1.
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