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

Ian D. Davis, Gregory A. Wiseman, Fook Thean Lee, Denise N. Gansen, Wendie Hopkins, Anthony T. Papenfuss, Zhanqi Liu, Timothy J. Moynihan, Gary A. Croghan, Alex A. Adjei, Eric W. Hoffman, James N. Ingle, Lloyd J. Old, Andrew M. Scott

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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/m2 were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace 131I-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/m2 of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.

Original languageEnglish
JournalCancer Immunity
Publication statusPublished - 17 Aug 2007


  • cG250
  • Chimeric antibody
  • Human CA9 protein
  • Phase I clinical trial
  • Renal cell carcinoma

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