A phase I clinical study of VB4-845: Weekly intratumoral administration of an anti-EpCAM recombinant fusion protein in patients with squamous cell carcinoma of the head and neck

Original Research

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Authors: Glen C MacDonald, Michèle Rasamoelisolo, Joycelyn Entwistle, Jeannick Cizeau, Denis Bosc, et al

Published Date June 2008 Volume 2008:2 Pages 105 - 114

DOI: http://dx.doi.org/10.2147/DDDT.S3442

Glen C MacDonald¹, Michèle Rasamoelisolo¹, Joycelyn Entwistle¹, Jeannick Cizeau¹, Denis Bosc¹, Wendy Cuthbert², Mark Kowalski², Maureen Spearman¹, Nick Glover²

¹Viventia Biotech Inc., Winnipeg, Manitoba, Canada; ²Viventia Biotech Inc., Mississauga, Ontario, Canada

Abstract: VB4-845 is a scFv-Pseudomonas exotoxin A fusion construct that targets epithelial cell adhesion molecule (EpCAM). A phase I trial was conducted to determine the maximum tolerated dose (MTD) of VB4-845 when administered as weekly intratumoral (IT) injections to patients with squamous cell carcinoma of the head and neck (SCCHN). Secondary objectives included the evaluation of the safety, tolerability, pharmacokinetic profile, and immunogenicity, and a preliminary assessment of tumor response. Twenty patients with advanced, recurrent SCCHN were treated weekly for four weeks in ascending dose cohorts of 100, 200, 330, 500, 700, and 930 µg. The MTD was established as 930 µg with a dose limiting toxicity of elevated liver enzymes in two of five patients. VB4-845 therapy was well tolerated with common treatment-related adverse events of injection site reactions, fever, gastrointestinal disorders, and elevated liver enzyme levels. All patients developed antibodies to VB4-845 by the end of the study, but only seven patients had neutralizing antibodies. Preliminary efficacy data found 87.5% of EpCAM-positive patients had a positive response to VB4-845 therapy. Noninjected dermal metastases were also resolved in one patient. VB4-845 IT therapy is safe and feasible and warrants further clinical evaluation for the treatment of SCCHN.

Keywords: EpCAM, phase I, immunotoxin, head and neck cancer, VB4-845