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Open Access Research

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

Antoni Ribas1*, Jason A Chesney2, Michael S Gordon3, Amy P Abernethy4, Theodore F Logan5, David H Lawson6, Bartosz Chmielowksi1, John A Glaspy1, Karl Lewis7, Bo Huang8, Erjian Wang8, Poe-Hirr Hsyu8, Jesus Gomez-Navarro89, Diana Gerhardt8, Margaret A Marshall8 and Rene Gonzalez7

Author Affiliations

1 Division of Hematology-Oncology, 11-934 Factor Building, Jonsson Comprehensive Cancer Center at the University of California Los Angeles, Los Angeles, CA 90095-1782, USA

2 James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

3 Premiere Oncology of Arizona, Scottsdale, AZ, USA

4 Duke University, Durham, NC, USA

5 Indiana University, Indianapolis, IN, USA

6 Emory University, Atlanta, GA, USA

7 University of Colorado, Aurora, CO, USA

8 Pfizer Inc., Groton, CT, La jolla, CA, USA

9 Millennium-Takeda, Boston, Massachusetts, USA

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Journal of Translational Medicine 2012, 10:236  doi:10.1186/1479-5876-10-236

Published: 21 November 2012

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).

Keywords:
Melanoma; Tremelimumab; CTLA4