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Phase I Dose-Escalation Study of the Anti-CD70 Antibody ARGX-110 in Advanced Malignancies.
Aftimos, Philippe; Rolfo, Christian; Rottey, Sylvie; Offner, Fritz; Bron, Dominique; Maerevoet, Marie; Soria, Jean-Charles; Moshir, Mahan; Dreier, Torsten; Van Rompaey, Luc; Michot, Jean-Marie; Silence, Karen; Hultberg, Anna; Gandini, Domenica; de Haard, Hans; Ribrag, Vincent; Peeters, Marc; Thibault, Alain; Leupin, Nicolas; Awada, Ahmad.
Afiliação
  • Aftimos P; Institut Jules Bordet, Brussels, Belgium.
  • Rolfo C; University Hospital Antwerp, Edegem, Belgium.
  • Rottey S; University Hospital Ghent, Ghent, Belgium.
  • Offner F; University Hospital Ghent, Ghent, Belgium.
  • Bron D; Institut Jules Bordet, Brussels, Belgium.
  • Maerevoet M; Institut Jules Bordet, Brussels, Belgium.
  • Soria JC; Institut Gustave Roussy, Villejuif, France.
  • Moshir M; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Dreier T; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Van Rompaey L; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Michot JM; Institut Gustave Roussy, Villejuif, France.
  • Silence K; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Hultberg A; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Gandini D; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • de Haard H; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Ribrag V; Institut Gustave Roussy, Villejuif, France.
  • Peeters M; University Hospital Antwerp, Edegem, Belgium.
  • Thibault A; argenx BVBA, Zwijnaarde (Ghent), Belgium.
  • Leupin N; argenx BVBA, Zwijnaarde (Ghent), Belgium. nleupin@argenx.com.
  • Awada A; Institut Jules Bordet, Brussels, Belgium.
Clin Cancer Res ; 23(21): 6411-6420, 2017 Nov 01.
Article em En | MEDLINE | ID: mdl-28765328
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-emergent adverse events (TEAE). The most common TEAE were fatigue 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. Clin Cancer Res; 23(21); 6411-20. ©2017 AACR.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-Idiotípicos / Ligante CD27 / Anticorpos Monoclonais / Neoplasias Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-Idiotípicos / Ligante CD27 / Anticorpos Monoclonais / Neoplasias Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article