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Title
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Phase I dose-escalation study of the anti-CD70 antibody ARGX-110 in advanced malignancies
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Author
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Abstract
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| Purpose: The purpose of this study was to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of ARGX-110, a glyco-engineered monoclonal antibody, targeting CD70, in patients with CD70 expressing advanced malignancies. Experimental Design: Dose escalation with a sequential 3-3 design was performed in five steps at the 0.1, 1, 2, 5, and 10 mg/kg dose levels (N = 26). ARGX-110 was administered intravenously every 3 weeks until progression or intolerable toxicity. Dose-limiting toxicity was evaluated in the 21 days following the first ARGX-110 administration (Cycle 1). Samples for pharmacokinetics and pharmacodynamics were collected. Results: Dose-limiting toxicity was not observed and the maximum tolerated dose was not reached. ARGX-110 was generally well tolerated, with no dose-related increase in treatment-emer- and drug related infusion-related reactions (IRR). Of the 20 SAEs reported, five events, all IRRs, were considered related to ARGX-110. ARGX-110 demonstrates dose proportionality over the dose range 1 to 10 mg/kg, but not at 0.1 mg/kg and a terminal half-life of 10 to 13 days. The best overall response was stable disease (14/26) in all 26 evaluable patients with various malignancies and the mean duration of treatment was 15 weeks. No dose-response related antitumor activity was observed, but biomarker readouts provided signs of biological activity, particularly in patients with hematologic malignancies. Conclusions: This dose-escalation phase I trial provides evidence of good tolerability of ARGX-110, pharmacokinetics, and preliminary antitumor activity at all dose levels in generally heavily pretreated patients with advanced CD70-positive malignancies. (C) 2017 AACR. |
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Language
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English
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Source (journal)
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Clinical cancer research. - Philadelphia, Pa, 1995, currens
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Publication
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Philadelphia, Pa
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Association for Cancer Research
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2017
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ISSN
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1078-0432
[print]
1557-3265
[online]
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DOI
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10.1158/1078-0432.CCR-17-0613
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Volume/pages
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23
:21
(2017)
, p. 6411-6420
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ISI
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000414165200006
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Pubmed ID
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28765328
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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