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Phase IA/II,multicentre, open‐label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non‐Hodgkin or Hodgkin lymphoma |
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| Authors: | 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 |
| Affiliation: | 1. University of Texas MD Anderson Cancer Center, , Houston, TX, USA;2. Jewish General Hospital, McGill University, , Montreal, QC, Canada;3. Division of Medical Oncology and Hematology, Princess Margaret Hospital, , Toronto, ON, Canada;4. Institut de Cancérologie de l'Ouest, , Nantes, France;5. Cancer Research Institute, Seoul National University College of Medicine, , Seoul, Korea;6. Department of Haematology, University Hospital of Leuven, , Leuven, Belgium;7. IRCCS National Cancer Institute, University of Milan, , Milan, Italy;8. Center for Lymphoma, Massachusetts General Hospital Cancer Center, , Boston, MA, USA;9. Department of Haematology, Ghent University Hospital, , Ghent, Belgium;10. University Hospital of Cologne, , Cologne, Germany;11. Department of Cancer Studies and Molecular Medicine, University of Leicester, , Leicester, UK;12. Novartis Pharmaceuticals Corporation, , East Hanover, NJ, USA;13. Memorial Sloan‐Kettering Cancer Center, , New York, NY, USA;14. Dana‐Farber Cancer Institute, , Boston, MA, USA |
| 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. |
| Keywords: | non‐Hodgkin lymphoma Hodgkin lymphoma monoclonal antibodies |