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.
Written by:
Morris MJ, Eisenberger MA, Pili R, Denmeade SR, Rathkopf D, Slovin SF, Farrelly J, Chudow JJ, Vincent M, Scher HI, Carducci MA. Are you the author?
Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York.
Reference: Ann Oncol. 2012 May 2. Epub ahead of print.
doi: 10.1093/annonc/mds078
PubMed Abstract
PMID: 22553195
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