Investigational New Drugs

, Volume 29, Issue 5, pp 996–1003 | Cite as

A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

  • Benoit You
  • Anthony Brade
  • Joao M. Magalhaes
  • Lillian L. Siu
  • Amit Oza
  • Sonya Lovell
  • Lisa Wang
  • David W. Hedley
  • Leonardo V. Nicacio
  • Eric X. Chen


Purpose: Nimotuzumab is a humanized monoclonal antibody which inhibits the ligand-dependent activation of epidermal growth factor receptor (EGFR). We conducted a phase I trial to assess the pharmacodynamic (PD) effects of escalating doses of nimotuzumab administered alone in patients with advanced solid cancers patients. Experimental design: Patients were treated with escalating doses of weekly intravenous nimotuzumab at doses ranging between 100 and 800 mg. Tumor and skin biopsies were done before start of treatment and repeated 3 weeks after to assess immunohistochemical expression of EGFR and its downstream components. Results: Seventeen patients were enrolled, including 1 patient never treated. Although 1 dose-limiting-toxicity (DLT) was observed at 100 mg (grade 3 fatigue), nimotuzumab dose was escalated to 800 mg with no other DLT. No grade 4 toxicity was observed. Only 3 patients developed a grade 1 acneiform rash (18.7%). One patient achieved a partial response (6.2%) and 8 patients had stable disease (50.0%). The median TTP was 2.4 months. No significant changes in EGFR, AKT, ERK and Ki67 immuno-stainings were observed between pre- and on-treatment tumor or skin biopsies. Conclusion: Nimotuzumab could be safety administered up to 800 mg with manageable toxicity. No relationships were found between pharmacodynamic effects on EGFR downstream signaling pathways and drug efficacy or toxicity.


Nimotuzumab Antibodies Monoclonal Clinical Trial, Phase I Epidermal growth factor receptor 



Benoit You received academic grants from Académie Française (Bourse J. Walter-Zellidja) and from Centre Léon Bérard (Bourse M. Clavel).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Benoit You
    • 1
  • Anthony Brade
    • 1
  • Joao M. Magalhaes
    • 1
    • 2
  • Lillian L. Siu
    • 1
  • Amit Oza
    • 1
  • Sonya Lovell
    • 1
  • Lisa Wang
    • 1
  • David W. Hedley
    • 1
    • 2
  • Leonardo V. Nicacio
    • 3
  • Eric X. Chen
    • 1
    • 4
  1. 1.Department of Medical Oncology and Hematology, Princess Margaret HospitalUniversity Health NetworkTorontoCanada
  2. 2.Ontario Cancer Institute, and Department of Laboratory Medicine and PathologyUniversity of TorontoTorontoCanada
  3. 3.YM BioSciences Inc.MississaugaCanada
  4. 4.Department of Medical Oncology and HematologyPrincess Margaret HospitalTorontoCanada

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