Boosting long-term immune responses to sipuleucel-T (sip-T) by retreatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Authors

Tomasz M. Beer

Tomasz M. Beer

Knight Cancer Institute, Oregon Health & Science University, Portland, OR

Tomasz M. Beer , John Corman , Raymond S. Lance , Dwayne Campogan , Tuyen Vu , Heather Haynes , Nancy N. Chang , Nadeem Anwar Sheikh , Brendan D. Curti

Organizations

Knight Cancer Institute, Oregon Health & Science University, Portland, OR, Virginia Mason Medical Center, Seattle, WA, Eastern Virginia Medical School, Norfolk, VA, Dendreon Pharmaceuticals, Inc., Seattle, WA, Dendreon Corporation, Seattle, WA, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR

Research Funding

Pharmaceutical/Biotech Company

Background: Sip-T, an autologous cellular immunotherapy for asymptomatic/minimally symptomatic mCRPC, induces immune responses to target antigens prostatic acid phosphatase (PAP) and PA2024, a recombinant protein of PAP and granulocyte macrophage colony-stimulating factor. Immune responses with sip-T correlate with overall survival. PROTECT (phase 3 NCT00779402) assessed sip-T in biochemically recurrent androgen-dependent PC. PROTECT pts developing mCRPC were eligible for P10-1 (phase 2 NCT01338012). Methods: PROTECT pts (sip-T arm) were retreated with sip-T in mCRPC. Antigen presenting cell (APC) activation (CD54 molecule ratio after and before culture with PA2024), cellular (PA2024/PAP ELISPOT; T cell proliferation) and humoral responses were assessed and compared with treatment-naïve mCRPC pts (IMPACT NCT00065442; STAMP NCT01487863; STRIDE NCT01981122). Results: Caucasian men (n=8), median follow-up 9.2 y and age 74 y, had an ECOG PS of 0 (75%) or 1. Median APC activation with sip-T infusion 1 was ~3-fold higher in P10-1 (20; n=7) vs treatment-naïve mCRPC pts (7; n=447). In P10-1, high magnitude cellular and humoral responses were seen at baseline (BL) (Table). Immune memory was heterogeneous, strong BL humoral and/or robust cellular memory was observed. Sip-T boosted PA2024/PAP cellular and humoral responses (Table). Immune responses were maintained up to wk 52, and were higher over time vs 1st time treated mCRPC pts. Conclusions: Sip-T in an earlier disease setting generated sustained antigen-specific immune memory lasting up to 10 y. Consistent with vaccine-induced immune responses, sip-T retreatment rapidly boosted both cellular and humoral antigen-specific responses in mCRPC pts. Clinical trial information: NCT01338012

Endpoint median (range)P10-1 (n=7)
mCRPC pts (n=100–118)
BLWk 6BLWk 6
ELISPOT count(per 300,000 PBMC)
    PA202443 (0–362)249 (0–718)1 (0–66)16 (0–503)
    PAP48 (0–477)65 (4–643)0 (0–103)1 (0–398)
Proliferation stimulation index
    PA202430 (1–52)26 (1–118)1 (0–24)10 (1–90)
    PAP6 (1–28)7 (1–19)1 (0–100)1 (0–96)
IgG + IgM antibody titers x103
    PA202426 (0–205)410 (1–410)*1 (0–410)51 (0–410)
    PAP6 (0–51)51 (1–410)*2 (0–410)26 (0–410)

*p<0.05 vs BL

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Abstract Details

Meeting

2017 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer,Prostate Cancer

Sub Track

Prostate Cancer - Advanced Disease

Clinical Trial Registration Number

NCT01338012

Citation

J Clin Oncol 35, 2017 (suppl 6S; abstract 196)

DOI

10.1200/JCO.2017.35.6_suppl.196

Abstract #

196

Poster Bd #

G25

Abstract Disclosures

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