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

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 toxi...

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Bibliographic Details
Published in:Cancer immunity 2007-08, Vol.7, p.13
Main Authors: Davis, Ian D, Wiseman, Gregory A, Lee, Fook-Thean, Gansen, Denise N, Hopkins, Wendie, Papenfuss, Anthony T, Liu, Zhanqi, Moynihan, Timothy J, Croghan, Gary A, Adjei, Alex A, Hoffman, Eric W, Ingle, James N, Old, Lloyd J, Scott, Andrew M
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1424-9634