A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer Journal Article
| Authors: | Morris, M. J.; Eisenberger, M. A.; Pili, R.; Denmeade, S. R.; Rathkopf, D.; Slovin, S. F.; Farrelly, J.; Chudow, J. J.; Vincent, M.; Scher, H. I.; Carducci, M. A. |
| Article Title: | A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer |
| Abstract: | Background: This first-in-human phase I/IIA study was designed to evaluate the safety and pharmacokinetics (PKs) of AGS-PSCA a fully human monoclonal antibody directed to prostate stem cell antigen (PSCA) in progressive castration-resistant prostate cancer. Patients and methods: Twenty-nine patients were administered infusions of AGS-PSCA (1-40 mg/kg) every 3 weeks for 12 weeks; 18 final patients received a 40-mg/kg loading dose followed by 20-mg/kg repeat doses. Primary end points were safety and PK. Immunogenicity, antitumor activity and circulating tumor cells were also evaluated. Results: No drug-related serious adverse events were noted. Dose escalation stopped before reaching the maximum tolerated dose as target concentrations were achieved. Drug levels accumulated linearly with dose and the mean terminal half-life was 2-3 weeks across dose levels. The 40-mg/kg loading dose followed by repeated 20-mg/kg doses yielded serum drug concentrations above the projected minimum therapeutic threshold after two to three doses without excessive drug accumulation or toxicity. Significant antitumor effects were not seen. Conclusions: A 40-mg/kg loading dose followed by 20-mg/kg infusions every 3 weeks is the recommended phase II dose of AGS-PSCA. PSCA is a promising drug target and studies in prostate and other relevant solid tumors are planned. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | prostate cancer; targeted therapy; prostate stem cell antigen |
| Journal Title: | Annals of Oncology |
| Volume: | 23 |
| Issue: | 10 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2012-10-01 |
| Start Page: | 2714 |
| End Page: | 2719 |
| Language: | English |
| DOI: | 10.1093/annonc/mds078 |
| PROVIDER: | scopus |
| PMCID: | PMC3457748 |
| PUBMED: | 22553195 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 2 November 2012" - "Art. No.: mds078" - "CODEN: ANONE" - "Source: Scopus" |
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