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

Details

Serval ID
serval:BIB_09D77DAB9017
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours.
Journal
European Journal of Cancer
Author(s)
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.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
2013
Volume
49
Number
1
Pages
35-44
Language
english
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 3weeks. A subgroup of patients also received 300mg/m(2) 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 0.9mg/kg, and nine were treated at doses of 0.45 and 0.6mg/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 0.9mg/kg dose-level; the MTD was 0.6mg/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 0.6mg/kg. The recommended phase II dose was 0.45-0.6mg/kg. Selectikine had a favourable safety profile and induced biological effects typical for IL-2.
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2013 18:11
Last modification date
20/08/2019 12:31
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