775P - A randomized phase 2 study evaluating optimal sequencing of sipuleucel-T (sip-T) and androgen deprivation therapy (ADT) in biochemically-recurrent...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Cancer Immunology and Immunotherapy
Presenter Charles Drake
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors C. Drake1, A.S. Kibel2, G.W. Adams3, L.I. Karsh4, A. Elfiky5, N.D. Shore6, N. Vogelzang7, J. Corman8, R.C. Tyler9, C. McCoy9, T. Devries9, N. Sheikh10, E.S. Antonarakis11
  • 1Oncology, Immunology, And Urology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Brady Urological Institute, 21287 - Baltimore/US
  • 2Urologic Surgery, Brigham and Women’s Hospital, Harvard University, 02115 - Boston/US
  • 3Urology, Urology Centers of Alabama, 35209 - Homewood/US
  • 4Clinical Research, The Urology Center of Colorado, Denver/US
  • 5Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 6Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 7Medical Oncology, US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas/US
  • 8Urology, Virginia Mason Medical Center, Seattle/US
  • 9Medical Affairs, Dendreon Corporation, Seattle/US
  • 10Research And Development, Dendreon Corporation, Seattle/US
  • 11Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 21287 - Baltimore/US

Abstract

Aim

Sip-T is an autologous cellular immunotherapy targeting prostatic acid phosphatase (PAP) approved by the US FDA and EMA for treatment of certain patients with asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer based on a 22% reduction in risk of death in the IMPACT trial. Predictive markers of survival benefit from immunotherapy are needed. Eosinophil counts correlated with humoral response and survival in previous trials of sip-T; here we assess T cell proliferation and variables correlating with immune response in the STAND trial.

Methods

STAND evaluates optimal sequencing of sip-T and ADT in men with BRPC at high risk for metastases. Men (N = 68) were randomized 1:1 to Arm 1: sip-T followed by ADT (2 wks after 3rd infusion) or Arm 2: ADT (3 mo lead-in) followed by sip-T. All men had 3 doses of sip-T and 12 mos of ADT. Primary endpoint: cellular immune response. Secondary endpoints: humoral/cytokine responses, product parameters, safety. Spearman's correlations (r) were used to assess the relationship between maximal humoral response, cumulative product parameters, and maximal post-baseline eosinophil count.

Results

65 men have been followed for ≥9 mos post-ADT. Sip-T induced robust immune responses to PA2024 and PAP (T cell memory responses and ELISA antibody responses to PAP and PA2024, a recombinant protein comprising PAP fused to granulocyte-macrophage colony-stimulating factor) in both arms. Variables that correlated with antibody responses included cumulative total nucleated cell (TNC) count (PA2024, P = 0.03; PAP, P = 0.08) and maximum eosinophil count after sip-T treatment (PA2024, P = 0.06; PAP, P = 0.02). Antigen-specific T cell proliferation increased after the 2nd sip-T infusion and persisted to 26 wks.

Conclusions

Consistent with other studies, sip-T induced a robust, long-term cellular immune response. Although not different between arms, cumulative TNC count and maximum eosinophil count after sip-T may be markers associated with humoral response, and warrant further study.

Disclosure

C.G. Drake: Research funding: Aduro, Bristol Myers Squibb Consultant/advisory role: Bristol Myers Squibb, Dendreon, Janssen, Pfizer, Roche; A.S. Kibel: Advisory Board for Dendreon, Sanofi, and Myraid; G.W. Adams: Speakers bureau for Dendreon & Amgen; L.I. Karsh: Consultant/advisor: Dendreon Investigator: Dendreon Meeting participant/lecturer: Dendreon Scientific study/trial: Dendreon; N.D. Shore: Research/consultant for Algeta, Astellas, Bayer, Pfizer, Millenium, Janssen, Medivation, Sanofi

N.J. Vogelzang: Dendreon speakers bureau and research funding from Dendreon; J.M. Corman: Honoraria and Research Funding for Dendreon; R.C. Tyler, C. McCoy, T. Devries and N. Sheikh: Dendreon Corporation: Employee and Stock Holder; E.S. Antonarakis: Dendreon advisory board and Dendreon research funding. All other authors have declared no conflicts of interest.