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

• Type of Material: Article
• Authors: Antoni Ribas, University of California Los Angeles; Jason A. Chesney, University of Louisville; Michael S. Gordon, Premiere Oncology of Arizona; Amy P. Abernethy, Duke University; Theodore F. Logan, Indiana University; David Lawson, Emory University; Bartosz Chmielowksi, University of California Los Angeles; John A. Glaspy, University of California Los Angeles; Karl Lewis, University of Colorado; Bo Huang, Pfizer Inc; Erjian Wang, Pfizer Inc; Poe-Hirr Hsyu, Pfizer Inc; Jesus Gomez-Navarro, Pfizer Inc; Diana Gerhardt, Pfizer Inc; Margaret A. Marshall, Pfizer Inc; Rene Gonzalez, University of Colorado
• Language: English
• Date: 2012-11-21
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Ribas et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/1479-5876-10-236
• Title of Journal or Parent Work: Journal of Translational Medicine
• ISSN: 1479-5876
• Volume: 10
• Issue: 1
• Start Page: 236
• End Page: 236
• Grant/Funding Information: Support for these studies was provided by Pfizer Inc.
• Keywords: Medicine, Research & Experimental; TRIAL; CTLA4; METASTATIC MELANOMA; Science & Technology; CTLA4 BLOCKADE; PHASE-II; Tremelimumab; RESPONSES; CP-675,206; MONOCLONAL-ANTIBODY; Life Sciences & Biomedicine; Melanoma; Research & Experimental Medicine; MEDICINE, RESEARCH & EXPERIMENTAL; CLINICAL DEVELOPMENT
• Research Categories: Health Sciences, Oncology

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).