title: Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion.
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).
authors.affiliation: 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. aribas@mednet.ucla.edu
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Jason A
authors.initials: JA
authors.lastname: Chesney
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Logan
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowksi
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: Karl
authors.initials: K
authors.lastname: Lewis
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Erjian
authors.initials: E
authors.lastname: Wang
authors.forename: Poe-Hirr
authors.initials: PH
authors.lastname: Hsyu
authors.forename: Jesus
authors.initials: J
authors.lastname: Gomez-Navarro
authors.forename: Diana
authors.initials: D
authors.lastname: Gerhardt
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Marshall
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000276:immunology*; D003710:Demography; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C520704:tremelimumab