Phase IA/II, multicentre, open‐label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non‐Hodgkin or Hodgkin lymphoma

Medientyp: E-Artikel
Titel: Phase IA/II, multicentre, open‐label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non‐Hodgkin or Hodgkin lymphoma
Beteiligte: Fanale, Michelle; Assouline, Sarit; Kuruvilla, John; Solal‐Céligny, Philippe; Heo, Dae S.; Verhoef, Gregor; Corradini, Paolo; Abramson, Jeremy S.; Offner, Fritz; Engert, Andreas; Dyer, Martin J. S.; Carreon, Daniel; Ewald, Brett; Baeck, Johan; Younes, Anas; Freedman, Arnold S.
Erschienen: Wiley, 2014
Erschienen in: British Journal of Haematology
Sprache: Englisch
DOI: 10.1111/bjh.12630
ISSN: 1365-2141; 0007-1048
Schlagwörter: Hematology
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Beschreibung: <jats:title>Summary</jats:title><jats:p>Despite advancements in the treatment of non‐Hodgkin lymphoma (<jats:styled-content style="fixed-case">NHL</jats:styled-content>) and <jats:styled-content style="fixed-case">H</jats:styled-content>odgkin lymphoma (<jats:styled-content style="fixed-case">HL</jats:styled-content>), patients continue to relapse and thus a need for new targeted therapies remains. The <jats:styled-content style="fixed-case">CD</jats:styled-content>40 receptor is highly expressed on neoplastic <jats:styled-content style="fixed-case">B</jats:styled-content> cells and activation leads to enhanced proliferation and survival. Lucatumumab (<jats:styled-content style="fixed-case">HCD</jats:styled-content>122) is a fully human antagonistic <jats:styled-content style="fixed-case">CD</jats:styled-content>40 monoclonal antibody. A phase <jats:styled-content style="fixed-case">IA</jats:styled-content>/<jats:styled-content style="fixed-case">II</jats:styled-content> study was designed to determine the maximum tolerated dose (<jats:styled-content style="fixed-case">MTD</jats:styled-content>) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the <jats:styled-content style="fixed-case">MTD</jats:styled-content> was the primary objective of the phase <jats:styled-content style="fixed-case">IA</jats:styled-content> dose escalation portion and clinical response was the primary objective of the phase <jats:styled-content style="fixed-case">II</jats:styled-content> dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8‐week cycle. <jats:styled-content style="fixed-case">MTD</jats:styled-content> was determined at 4 mg/kg of lucatumumab. A total of 111 patients with <jats:styled-content style="fixed-case">NHL</jats:styled-content> (<jats:italic>n</jats:italic> = 74) and <jats:styled-content style="fixed-case">HL</jats:styled-content> (<jats:italic>n</jats:italic> = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (<jats:styled-content style="fixed-case">FL</jats:styled-content>) and marginal zone lymphoma of mucosa‐associated lymphatic tissue (<jats:styled-content style="fixed-case">MZL</jats:styled-content>/<jats:styled-content style="fixed-case">MALT</jats:styled-content>) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of <jats:styled-content style="fixed-case">CD</jats:styled-content>40 warrants further investigation.</jats:p>
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