943P - OPENACT: phase 2, open-label study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Immunotherapy
Therapy
Presenter John Corman
Authors J. Corman1, N. Dawson2, S. Hall3, C. Nabhan4, A. Ferrari5, A.J. Armstrong6, M.I. Murdock7, F. Stewart8, N. Sheikh9, D.P. Petrylak10
  • 1Surgery, Virginia Mason Medical Center, 98111 - Seattle/US
  • 2Medical Oncology, Georgetown University, Washington/US
  • 3Urology, Mount Sinai School of Medicine, New York/US
  • 4Hematology And Medical Oncolgoy, Advocate Lutheran General Hospital, Park Ridge/US
  • 5Medicine, New York University Cancer Center, New York/US
  • 6Medical Oncology, Duke Cancer Institute, Duke University, Durham/US
  • 7Urology, Murdock Urology Associates, Greenbelt/US
  • 8Biometrics, Dendreon Corporation, Seattle/US
  • 9Clinical Immunology, Dendreon Corporation, Seattle/US
  • 10Medical Oncology, Columbia University Medical Center, 10032 - New York/US

Abstract

Background

Sipuleucel-T is an FDA-approved autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic mCRPC. In the Phase 3 IMPACT trial, sipuleucel-T showed a 22% reduction in risk of death (p = 0.032) and a 4.1-month median OS improvement (25.8 vs 21.7 months) compared with control. OpenACT (P09-1; NCT00901342) is a Phase 2 open-label study to further evaluate the safety and immune responses of sipuleucel-T in patients (pts) with mCRPC.

Methods

Pts received sipuleucel-T at 2-week (wk) intervals for a total of 3 infusions. Sipuleucel-T is manufactured from autologous PBMCs isolated by leukapheresis at wks 0, 2 and 4, and activated with PA2024 (a recombinant fusion protein composed of prostatic acid phosphatase [PAP] linked to GM-CSF). Cell activation is measured by upregulation of the costimulatory molecule CD54. The primary endpoint was to evaluate the magnitude of immune responses to sipuleucel-T treatment.

Results

From October 2009–June 2010, 104 pts were enrolled; 101 pts received ≥1 leukapheresis and 98 pts received ≥1 infusion (safety population). Pts who had received prior docetaxel (D; 29.3% of enrolled pts) had a higher baseline prostate-specific antigen (90 vs 40ng/mL) and a greater proportion with a time from diagnosis of ≥6 years (93.5% vs 68.7%) compared with pts with no prior D exposure. Consistent with previous studies, CD54 upregulation and post-culture cytokine levels were significantly greater at wk2 and wk4 compared with wk0 (p < 0.05). At wk 6, PAP2024 and PAP-specific humoral and T cell proliferative responses were significantly increased from baseline. Pts without prior exposure to D had higher CD54 cell counts and total nucleated cell count (TNC) than pts who had received prior D. The most common AEs were infusion-related: fatigue (30.6%), nausea (18.4%) and chills (17.3%).

Discussion

Sipuleucel-T generates antigen-specific immune responses in patients with and without prior D exposure. However, product characteristics suggest that patients without prior D may generate sip-T products with higher TNC, which has previously been shown to correlate with prolonged survival, supporting earlier use in the mCRPC treatment paradigm.

Disclosure

J. Corman: On the Board of Directors for Benaroya Research Institute and employee of Virginia Mason Medical Center,

N. Dawson: Corporate sponsored research for Dendreon Corporation, and participation in Speakers Bureau also for Dendreon Corporation,

S. Hall: Corporate sponsored research for Dendreon and Medivation,

C. Nabhan: Participation in corporate sponsored research and speakers bureau,

A. Ferrari: Participation in advisory boards,

A.J. Armstrong: Advisory boards for Bristol Myers Squibb, Bayer, Amgen; sponsored research for Dendreon, Sanofi Aventis, Medivation, Eli Lilly, Pfizer, Novartis, Janssen Biotech, Kanglaite Active Biotech/Ipsen; speaker for Dendreon, Sanofi Aventis, Amgen, Pfizer,

F. Stewart: Employee and stock ownership in Dendreon Corporation,

N. Sheikh: Employee of and stock ownership in Dendreon Corporation,

D.P. Petrylak: Advisory boards for Amgen, Bayer, Pfizer, Ferring, Millenium, Novartis, Dendreon, Johnson and Johnson, GlaxoSmithKline; sponsored research Celgene, Dendreon, Sanofi, Pfizer, AstraZeneca, GlaxoSmithKline, Rogesen Institute, Boheringer Ingelheim,

All other authors have declared no conflicts of interest.