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
Cancer Immunology and Immunotherapy
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.