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).

Authors

null

Emmanuel S. Antonarakis

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD

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

Organizations

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Urology Centers of Alabama, Homewood, AL, The Urology Center of Colorado, Denver, CO, Brigham and Women's Hospital, Harvard University, Boston, MA, Carolina Urologic Research Center, Myrtle Beach, SC, US Oncology Research, Comprehensive Cancer Centers of Nevada, Medical Oncology, Las Vegas, NV, Dendreon Corporation, Seattle, WA

Research Funding

Pharmaceutical/Biotech Company

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

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Abstract Details

Meeting

2015 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session A: Prostate Cancer

Track

Prostate Cancer

Sub Track

Prostate Cancer - Advanced Disease

Clinical Trial Registration Number

NCT01431391

Citation

J Clin Oncol 33, 2015 (suppl 7; abstr 171)

DOI

10.1200/jco.2015.33.7_suppl.171

Abstract #

171

Poster Bd #

H7

Abstract Disclosures