A phase I multiple dose, dose escalation study of cG250 monoclonal antibody in patients with advanced renal cell carcinoma

Cancer Immun. 2007 Aug 17;7:13.

Abstract

The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HACA during the second six-week cycle. PK analysis showed mean whole body and blood alpha and beta half-lives of cG250 of 18.99 +/- 6.84 and 180.19 +/- 86.68 hours, respectively. All patients had cG250 tumour localization by gamma camera imaging in week 1 and 5. One patient had a complete response, nine patients had stable disease, and three had progressive disease. One patient received 11 six-week cycles of treatment with no toxicity or HACA. In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / immunology*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / immunology*
  • Carcinoma, Renal Cell / diagnostic imaging
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy*
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Radionuclide Imaging
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • G250 monoclonal antibody
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases