A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer

M. J. Morris, M. A. Eisenberger, Roberto Pili, S. R. Denmeade, D. Rathkopf, S. F. Slovin, J. Farrelly, J. J. Chudow, M. Vincent, H. I. Scher, M. A. Carducci

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbermds078
Pages (from-to)2714-2719
Number of pages6
JournalAnnals of Oncology
Volume23
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Castration
Prostate
Prostatic Neoplasms
Stem Cells
Antigens
Pharmaceutical Preparations
Pharmacokinetics
Circulating Neoplastic Cells
Safety
Maximum Tolerated Dose
Half-Life
Monoclonal Antibodies
Serum
Neoplasms

Keywords

  • Prostate cancer
  • Prostate stem cell antigen
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Morris, M. J., Eisenberger, M. A., Pili, R., Denmeade, S. R., Rathkopf, D., Slovin, S. F., ... Carducci, M. A. (2012). A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer. Annals of Oncology, 23(10), 2714-2719. [mds078]. https://doi.org/10.1093/annonc/mds078

A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer. / Morris, M. J.; Eisenberger, M. A.; Pili, Roberto; Denmeade, S. R.; Rathkopf, D.; Slovin, S. F.; Farrelly, J.; Chudow, J. J.; Vincent, M.; Scher, H. I.; Carducci, M. A.

In: Annals of Oncology, Vol. 23, No. 10, mds078, 10.2012, p. 2714-2719.

Research output: Contribution to journalArticle

Morris, MJ, Eisenberger, MA, Pili, R, Denmeade, SR, Rathkopf, D, Slovin, SF, Farrelly, J, Chudow, JJ, Vincent, M, Scher, HI & Carducci, MA 2012, 'A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer', Annals of Oncology, vol. 23, no. 10, mds078, pp. 2714-2719. https://doi.org/10.1093/annonc/mds078
Morris MJ, Eisenberger MA, Pili R, Denmeade SR, Rathkopf D, Slovin SF et al. A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer. Annals of Oncology. 2012 Oct;23(10):2714-2719. mds078. https://doi.org/10.1093/annonc/mds078
Morris, M. J. ; Eisenberger, M. A. ; Pili, Roberto ; Denmeade, S. R. ; Rathkopf, D. ; Slovin, S. F. ; Farrelly, J. ; Chudow, J. J. ; Vincent, M. ; Scher, H. I. ; Carducci, M. A. / A phase I/IIA study of AGS-PSCA for castration-resistant prostate cancer. In: Annals of Oncology. 2012 ; Vol. 23, No. 10. pp. 2714-2719.
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