A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies
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Published on: August 11, 2017
Benoit You1, Anthony Brade, Joao M Magalhaes
1Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
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.
