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

Sanjay Goel, R. J. Bauer, K. Desai, A. Bulgaru, T. Iqbal, B. K. Strachan, G. Kim, Andreas Kaubisch, G. F. Vanhove, G. Goldberg, Sridhar Mani

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: ING-1 is a high-affinity, human engineered™ 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.

Original languageEnglish (US)
Pages (from-to)1704-1707
Number of pages4
JournalAnnals of Oncology
Volume18
Issue number10
DOIs
StatePublished - Oct 2007

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Pharmacokinetics
Monoclonal Antibodies
Safety
Pancreatitis
Neoplasms
Pharmaceutical Preparations
Immunotherapy
Colonic Neoplasms
Antibody Formation
Anti-Idiotypic Antibodies
Glycoproteins
Adenocarcinoma
Drug Therapy
Epithelial Cell Adhesion Molecule

Keywords

  • Cancer
  • EpCAM
  • ING-1
  • Pharmacokinetics
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineered™ monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors. / Goel, Sanjay; Bauer, R. J.; Desai, K.; Bulgaru, A.; Iqbal, T.; Strachan, B. K.; Kim, G.; Kaubisch, Andreas; Vanhove, G. F.; Goldberg, G.; Mani, Sridhar.

In: Annals of Oncology, Vol. 18, No. 10, 10.2007, p. 1704-1707.

Research output: Contribution to journalArticle

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abstract = "Background: ING-1 is a high-affinity, human engineered™ 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.",
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