A phase i dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours

Silke Gillessen, Ulrike S. Gnad-Vogt, Elisa Gallerani, Joachim Beck, Cristiana Sessa, Aurelius Omlin, Maria R. Mattiacci, Bernd Liedert, Daniel Kramer, Julien Laurent, Daniel E. Speiser, Roger Stupp*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: EMD 521873 (Selectikine), an immunocytokine comprising a DNA-targeting antibody, aimed at tumour necrosis, fused with a genetically modified interleukin-2 (IL-2) moiety, was investigated in this first-in-human phase I study. Methods: Patients had metastatic or locally advanced solid tumours failing previous standard therapy. Selectikine was administered as a 1-hour intravenous infusion on 3 consecutive days, every 3 weeks. A subgroup of patients also received 300 mg/m2 cyclophosphamide on day 1 of each cycle. Escalating doses of Selectikine were investigated with the primary objective of determining the maximum tolerated dose (MTD). Results: Thirty-nine patients were treated with Selectikine alone at dose levels from 0.075 to 0.9 mg/kg, and nine were treated at doses of 0.45 and 0.6 mg/kg in combination with cyclophosphamide. A dose-dependent linear increase of peak serum concentrations and area under curve was found. The dose-limiting toxicity was grade 3 skin rash at the 0.9 mg/kg dose-level; the MTD was 0.6 mg/kg. Rash and flu-like symptoms were the most frequent side-effects. No severe cardiovascular side-effects (hypotension or vascular leak) were observed. At all dose-levels, transient increases in total lymphocyte, eosinophil and monocyte counts were recorded. No objective tumour responses, but long periods of disease stabilisation were observed. Transient and non-neutralising Selectikine antibodies were detected in 69% of patients. Conclusions: The MTD of Selectikine with or without cyclophosphamide administered under this schedule was 0.6 mg/kg. The recommended phase II dose was 0.45-0.6 mg/kg. Selectikine had a favourable safety profile and induced biological effects typical for IL-2.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalEuropean Journal of Cancer
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Advanced solid tumours
  • Dose-escalation
  • EMD 521873
  • Phase I
  • Selectikine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gillessen, S., Gnad-Vogt, U. S., Gallerani, E., Beck, J., Sessa, C., Omlin, A., Mattiacci, M. R., Liedert, B., Kramer, D., Laurent, J., Speiser, D. E., & Stupp, R. (2013). A phase i dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours. European Journal of Cancer, 49(1), 35-44. https://doi.org/10.1016/j.ejca.2012.07.015