A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.

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Serval ID
serval:BIB_61FC394BA881
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.
Journal
BMC Cancer
Author(s)
Connor J.P., Cristea M.C., Lewis N.L., Lewis L.D., Komarnitsky P.B., Mattiacci M.R., Felder M., Stewart S., Harter J., Henslee-Downey J., Kramer D., Neugebauer R., Stupp R.
ISSN
1471-2407 (Electronic)
ISSN-L
1471-2407
Publication state
Published
Issued date
2013
Volume
13
Number
20
Pages
1-12
Language
english
Notes
Publication types: Journal ArticlePublication Status: epublish. PDF type: RESEARCH ARTICLE
Abstract
BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.
METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.
RESULTS: Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients.
CONCLUSION: The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles.
TRIAL REGISTRATION: http://NCT00132522.
Pubmed
Web of science
Open Access
Yes
Create date
12/04/2013 17:59
Last modification date
20/08/2019 14:18
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