943P - Openact: Phase 2, Open-Label Study of Sipuleucel-T in Metastatic Castrate-Resistant Prostate Cancer (MCRPC)

Abstract

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 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.