Randomized phase II study of sipuleucel-T (SipT) with or without radium-223 (Ra223) in men with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC)

• Published in: Journal of clinical oncology Vol. 38; no. 6_suppl; p. 130
• Main Authors: Marshall, Catherine Handy, Park, Jong Chul, DeWeese, Theodore L., King, Serina, Afful, Michaella, Hurrelbrink, Julia, Manogue, Charlotte, Cotogno, Patrick, Moldawer, Nancy P., Barata, Pedro C., Drake, Charles G., Posadas, Edwin M., Armstrong, Andrew J., Sartor, A. Oliver, Antonarakis, Emmanuel S.
• Format: Journal Article
• Language: English
• Published: 20.02.2020
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2020.38.6_suppl.130

Abstract only 130 Background: SipT-induced antigen-specific immune responses in mCRPC patients correlate with survival. Due to the immunomodulatory effects of radiopharmaceutical agents (e.g. enhancing tumor-antigen display), we hypothesized that combined use of Ra223 and SipT would augment SipT-related immune response and improve outcomes compared to SipT alone. Methods: Patients with asymptomatic mCRPC and bone-predominant mets, without visceral mets >1.0 cm, were randomized (1:1) to standard SipT alone or combined with 6 doses of Ra223 (NCT02463799). Men in the SipT+Ra223 arm received SipT between the 2nd and 3rd dose of Ra223. Clinical endpoints were radiographic/clinical PFS, PSA response (≥50% decline), AlkPhos response (≥30% decline), and safety. Immunologic endpoints were PA2024-specific T-cell proliferation 6 wks after the first SipT infusion, PA2024-specific ELISPOT response, PAP-specific proliferation and ELISPOT, humoral responses against both antigens, and antigen spread. Results: 32 men were randomized, 16 per arm. Baseline characteristics in SipT and SipT+Ra223 arms were matched with respect to age (median 70 vs 71 yrs), Gleason (8-10: 69% vs 69%), PSA (median 82 vs 72 ng/mL), AlkPhos (median 125 vs 125 U/L) and ECOG scores (≥1: 19% vs 31%). After median follow up of 5.3 (range 2.8–26.6) mo, median PFS was longer in the SipT+Ra223 arm (10.7 vs 3.1 mo; HR 0.35, 95% CI 0.15–0.81; P=0.02). Outcomes were also better in the SipT+Ra223 arm with respect to PSA responses (5/15=33% vs 0/14=0%; P=0.04) and AlkPhos responses (9/15=60% vs 1/15=7%; P=0.01). No safety concerns were observed with the combination (grade 3 AEs shown in the Table). Conclusions: SipT combined with Ra223 was associated with improved clinical outcomes compared to SipT alone. Since neither agent reliably induces PSA responses alone, these data suggest a synergistic effect of the combination. Immunologic endpoints will be presented at the meeting. Larger randomized studies of this combination are warranted. Clinical trial information: NCT02463799. [Table: see text]