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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)

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P145

https://doi.org/10.1186/2051-1426-3-S2-P145

  • Published:

Keywords

  • Androgen Receptor
  • Humoral Immune Response
  • Humoral Response
  • Enzalutamide
  • Cell Proliferative Response

Background

P12-2 (STRIDE; NCT01981122) is an ongoing, randomized, Phase II, open-label study evaluating concurrent vs sequential administration of the androgen receptor inhibitor, enz, with the autologous cellular immunotherapy, sip-T. The primary aim of this study is to determine if the order of sip-T and enz administration impacts immune responses to the immunizing antigen, PA2024, of sip-T.

Methods

Patients with asymptomatic or minimally symptomatic mCRPC were randomized 1:1 to receive 3 sip-T infusions with enz starting 2 weeks (wks) before (n=25, concurrent arm A) or 10 wks after (n=27, sequential arm B) sip-T initiation. Antigen-specific cellular and humoral immune responses were evaluated via interferon (IFN)-γ ELISPOT, cell proliferation, and antibody ELISA assays. In addition, the breadth of the humoral response to non-target antigens was also studied.

Results

T cell proliferative responses to PA2024 were significantly elevated at all post-baseline time points (p < 0.001) and were sustained through wk 26, including a >10-fold increase at wk 20 in both arms. Both arms showed a significant and sustained increase in IFN-γ ELISPOT response to PA2024 and humoral responses to PA2024 and PAP. Broadening of the humoral responses to non-target antigens PSA, LGALS3, LGALS8, KRAS, ERAS and KLK2 at all post-treatment time points was observed in both arms. Cytokines indicative of immune activation (including IFN-γ, interleukin-2, and tumor necrosis factor-α) were also elevated in both arms, at the 2nd and 3rd sip-T infusions. Adverse events were similar between arms.

Conclusions

Treatment of mCRPC subjects with enz administered concurrently with or subsequent to sip-T resulted in significant and sustained peripheral antigen-specific T cell and humoral immune responses through wk 26. Both treatment schedules led to similarly robust humoral antigen spread sustained through wk 26. These data suggest enz did not affect sip-T production, subsequent immune responses, or safety.

Trial registration

ClinicalTrials.gov identifier NCT01981122.

Authors’ Affiliations

(1)
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
(2)
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
(3)
University of Virginia Cancer Center, Charlottesville, VA, USA
(4)
Johns Hopkins University School of Medicine, Baltimore, MD, USA
(5)
Atlantic Urology Clinics, Myrtle Beach, SC, USA
(6)
Virginia Mason Cancer Institute, Seattle, WA, USA
(7)
Urology Associates, Nashville, TN, USA
(8)
Associated Medical Professionals of New York, Syracuse, NY, USA
(9)
Dendreon, Seattle, WA, USA
(10)
Yale Cancer Center, New Haven, CT, USA

Copyright

© Drake et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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