Antigen-specific immune responses through 24 months in the STAND trial: A randomized phase 2 study evaluating optimal sequencing of sipuleucel-T (sip-T) and androgen deprivation therapy (ADT) in biochemically-recurrent prostate cancer (BRPC). Academic Article

abstract

  • 171 Background: Sip-T is an autologous cellular immunotherapy targeting prostatic acid phosphatase (PAP), approved for treatment of asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer. STAND evaluates sequencing of sip-T and ADT in men with BRPC at high risk of metastases. Here we report interim assessments of cellular and humoral responses through 24 mos. Methods: Men (n=68)were randomized 1:1 to sip-T followed by ADT (2 wks after 3rd infusion; Arm 1) or ADT (3-mo lead-in) followed by sip-T (Arm 2). Product parameters (total nucleated cell [TNC] count, antigen presenting cell [APC] count, APC activation) were determined with each product manufacture. Cellular and humoral immune responses were analyzed through 24 mos with a repeated measures statistical model. Results: Sample size ranged 8–28 for cellular responses and 34–64 for humoral responses. PA2024 ELISPOT count increased vs baseline at most timepoints (p<0.05) and was lower in Arm 2 vs Arm 1 (p=0.015). PA2024 antigen-specific T-cell proliferation increased from baseline at all timepoints (p≤0.001) and was lower in Arm 2 vs Arm 1 (p<0.001). PA2024 antibody titers were similar between treatment arms (p=0.976). PA2024 antibody titer was significantly higher at the 3rd sip-T infusion visit and remained elevated at 24 mos (23 times higher on average vs baseline; p<0.001). A similar antibody titer profile was reported for PAP but of lesser magnitude. The number of immune responders (post-baseline antibody titer ≥25,600) was similar at any timepoint between arms (Arm 1: 30/34, 88.1%; Arm 2: 32/34, 94.1%; p=0.673). Higher cumulative TNC and baseline hemoglobin positively correlated with maximum PA2024 antibody titer response (p<0.05). Conclusions: Sip-T induced a robust immune response sustained to 24 mos in men with BRPC. Cellular response appeared to differ according to treatment sequence; humoral response was similar between treatment arms. Given its consistent association with the humoral response, cumulative TNC count may be a potential biomarker of response to sip-T. Clinical trial information: NCT01431391.

authors

  • Antonarakis, Emmanuel S.
  • Kibel, Adam S.
  • Adams, George W.
  • Karsh, Lawrence, MD, FACS, CPI
  • Elfiky, Aymen
  • Shore, Neal D.
  • Vogelzang, Nicholas J.
  • Corman, John M.
  • Tyler, Robert Claude
  • McCoy, Candice
  • DeVries, Todd
  • Sheikh, Nadeem A.
  • Drake, Charles G.

Publication Date

  • 2015

webpage

published in

Digital Object Identifier (DOI)

number of pages

  • 1

start page

  • 171

end page

  • 171

volume

  • 33

issue

  • 7_suppl