Immune response from STRIDE, a randomized, Phase II, open-label study of sipuleucel-T (sip-T) with concurrent vs sequential enzalutamide (enz) administration in metastatic castration-resistant prostate cancer (mCRPC)

Abstract

Background: In metastatic castration‐resistant prostate cancer (mCRPC), data are limited regarding optimal combinatorial or sequential use of available treatments. STRIDE (NCT01981122) is an ongoing, randomized, open‐label, phase 2 study evaluating concurrent vs sequential administration of the androgen receptor inhibitor enzalutamide (enz) with the autologous cellular immunotherapy sipuleucel‐T (sip‐T). Materials and Methods: Fifty‐two patients (pts) with asymptomatic or minimally symptomatic mCRPC were randomized 1:1 to receive 3 sip‐T infusions with enz beginning 2 wks before (n = 25, concurrent arm A) or 10 wks after (n = 27, sequential arm B) sip‐T initiation. The primary endpoint was peripheral T cell proliferation response to PA2024, the immunogen used to manufacture sip‐T. Secondary endpoints included interferon (IFN)‐ g ELISPOT and humoral immune responses to PA2024 and prostatic acid phosphatase (PAP), product parameters (total nucleated cell count, CD54+ cell counts, and antigen presenting cell activation [as measured by CD54 upregulation]), cytokine production, and adverse events (AEs). Clinical analyses included changes in prostate‐specific antigen (PSA) levels and eosinophil counts, which are known to be elevated after sip‐T treatment and correlate with immune responses and prostate cancer‐specific survival. Results through wk 52 are described. Results: The percentage of pts with >50% decrease in PSA was similar between arms (arm A: 80%; arm B: 81%). No differences were detected in the percentage of pts who had elevated eosinophil counts (arm A: 24%; arm B: 22%), which were similar to percentages previously reported in sip‐T‐treated patients. PA2024‐specific T cell proliferative and IFN‐g ELISPOT responses were significantly elevated at all post‐baseline time points (p < 0.001), sustained through wk 26, and observed in nearly all pts (arm A: 95.8%; arm B: 88.9%). Humoral responses to PA2024 and PAP were significantly increased in both arms through wk 52. Sip‐T product parameters and elevated cytokines indicative of immune activation (such as IFN‐g and interleukin‐2) were similar in both arms. AEs were observed in both arms (arm A: 88%; arm B: 100%), with grade >3 AE incidence similar between arms. Conclusions: Nearly all mCRPC pts receiving enz concurrently with or subsequent to sip‐T demonstrated significant and sustained peripheral T cell proliferation and IFN‐g ELISPOT responses to PA2024 through wk 26. Sustained humoral immune responses to PA2024 and PAP were observed through wk 52. The scheduling of enz relative to sip‐T did not produce differences in PSA reductions. These interim data suggest that enz does not impair sip‐T production, subsequent in vivo immune responses to sip‐T, or safety.