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.
  
  
  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.
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York; Department of Medicine, Weill Cornell Medical College, New York. Electronic address: morrism@mskcc.org.
authors.forename: M J
authors.initials: MJ
authors.lastname: Morris
authors.affiliation: Department of Oncology, Prostate Cancer and Chemical Therapeutics Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
authors.forename: M A
authors.initials: MA
authors.lastname: Eisenberger
authors.affiliation: Department of Oncology, Prostate Cancer and Chemical Therapeutics Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
authors.forename: R
authors.initials: R
authors.lastname: Pili
authors.affiliation: Department of Oncology, Prostate Cancer and Chemical Therapeutics Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
authors.forename: S R
authors.initials: SR
authors.lastname: Denmeade
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York; Department of Medicine, Weill Cornell Medical College, New York.
authors.forename: D
authors.initials: D
authors.lastname: Rathkopf
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York; Department of Medicine, Weill Cornell Medical College, New York.
authors.forename: S F
authors.initials: SF
authors.lastname: Slovin
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: J
authors.initials: J
authors.lastname: Farrelly
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: J J
authors.initials: JJ
authors.lastname: Chudow
authors.affiliation: Agensys Inc., An Affiliate of Astellas Pharma Inc., Santa Monica, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vincent
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York; Department of Medicine, Weill Cornell Medical College, New York.
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Department of Oncology, Prostate Cancer and Chemical Therapeutics Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
authors.forename: M A
authors.initials: MA
authors.lastname: Carducci
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000276:immunology; D006207:Half-Life; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology*; D009360:Neoplastic Cells, Circulating; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human