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Annals of Oncology Advance Access originally published online on August 9, 2007
Annals of Oncology 2007 18(10):1704-1707; doi:10.1093/annonc/mdm280
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© 2007 European Society for Medical Oncology

phase I and pharmacokinetics

Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineeredTM monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors

S. Goel1,2,*, R. J. Bauer4, K. Desai1,2, A. Bulgaru1,2, T. Iqbal1,2, B.-K. Strachan1,2, G. Kim2, A. Kaubisch1,2, G. F. Vanhove4, G. Goldberg1,3 and S. Mani1,2,*

1 Albert Einstein Cancer Center
2 Department of Oncology
3 Division of Gynecologic Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, New York
4 XOMA (US) LLC, Berkeley CA, USA

* Correspondence to: Dr S. Goel and Dr S. Mani, Weiler Hospital, Department of Oncology, 1825 Eastchester Road, Bronx, New York, NY 10461, USA. Tel: +1 718-904-2488; Fax: +1 718-904-2830; E-mail: sgoel{at}montefiore.org

Background: ING-1 is a high-affinity, human engineeredTM monoclonal antibody that recognizes a 40 kilodalton epithelial cell adhesion molecule (EpCAM) glycoprotein that is expressed in high levels on most adenocarcinomas and is an attractive target for immunotherapy.

Methods: ING-1 was administered subcutaneously weekly at doses between 0.1 and 2 mg/kg/week. Pharmacokinetic samples were drawn during weeks 1 and 6.

Results: Fourteen patients with advanced refractory cancer received a median of 6 (range 1–9) doses of ING-1. At 1 mg/kg, a 62-year-old man with colon cancer developed reversible grade 3 pancreatitis after the third dose. His plasma ING-1 levels were similar to the other two patients dosed at 1 mg/kg. Two patients dosed at 0.6 mg/kg experienced stable disease at 6 weeks. Peak drug levels increased with dose and time, suggesting drug accumulation with repeated dosing. Low human anti-human antibody response was noted in three of the 13 patients assessed and was directed towards the variable region of ING-1.

Conclusions: Weekly ING-1 administered subcutaneously was well tolerated at 0.6 mg/kg/week and further experience at this dose is warranted to demonstrate safety. The risk of pancreatitis and the marginal anti-tumor effect may preclude further monotherapy studies; however, combination studies with chemotherapy are warranted.

Key words: pharmacokinetics, Phase I, ING-1, EpCAM, cancer

Received for publication March 5, 2007. Revision received March 27, 2007. Accepted for publication May 9, 2007.


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