Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH 2), a beta integrin antagonist, in patients with solid tumours

M. E. Cianfrocca, K. A. Kimmel, J. Gallo, T. Cardoso, M. M. Brown, G. Hudes, N. Lewis, L. Weiner, G. N. Lam, S. C. Brown, D. E. Shaw, A. P. Mazar, R. B. Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg -1), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg -1, mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg -1, clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg -1 when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (≤280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy.

Original languageEnglish (US)
Pages (from-to)1621-1626
Number of pages6
JournalBritish Journal of Cancer
Volume94
Issue number11
DOIs
StatePublished - Jun 5 2006

Keywords

  • ATN-161
  • Angiogenesis
  • Phase 1 trial
  • α5β1 integrin
  • αvβ3 integrin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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