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

Michelle Fanale, Sarit Assouline, John Kuruvilla, Philippe Solal-Céligny, Dae S. Heo, Gregor Verhoef, Paolo Corradini, Jeremy S. Abramson, Fritz Offner, Andreas Engert, Martin J S Dyer, Daniel Carreon, Brett Ewald, Johan Baeck, Anas Younes, Arnold S. Freedman

Research output: Contribution to journalArticlepeer-review

Abstract

Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.

Original languageEnglish
Pages (from-to)258-265
Number of pages8
JournalBritish Journal of Haematology
Volume164
Issue number2
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Hodgkin lymphoma
  • Monoclonal antibodies
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Hematology

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