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 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.
Davis
Ian D
ID
Ludwig Institute for Cancer Research, Victoria, Australia. Ian.Davis@ludwig.edu.au
Wiseman
Gregory A
GA
Lee
Fook-Thean
FT
Gansen
Denise N
DN
Hopkins
Wendie
W
Papenfuss
Anthony T
AT
Liu
Zhanqi
Z
Moynihan
Timothy J
TJ
Croghan
Gary A
GA
Adjei
Alex A
AA
Hoffman
Eric W
EW
Ingle
James N
JN
Old
Lloyd J
LJ
Scott
Andrew M
AM
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C106533:G250 monoclonal antibody; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
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