Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer.

Autor: Drake CG; Columbia University Medical Center, New York, NY, USA. cdrake2@its.jnj.com.; Janssen Research & Development, Spring House, PA, USA. cdrake2@its.jnj.com., Pachynski RK; Washington University of St. Louis, St. Louis, MO, USA., Subudhi SK; The University of Texas MD Anderson Cancer Center, Houston, TX, USA., McNeel DG; University of Wisconsin Carbone Cancer Center, Madison, WI, USA., Antonarakis ES; Johns Hopkins Kimmel Medical Institute, Baltimore, MD, USA., Bauer TM; Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA., Lauer P; Aduro Biotech, Berkeley, CA, USA., Brockstedt D; Aduro Biotech, Berkeley, CA, USA., Patricia D; Janssen Research & Development, Spring House, PA, USA., Wade M; Janssen Research & Development, Spring House, PA, USA., Zudaire E; Janssen Research & Development, Spring House, PA, USA., Bandyopadhyay N; Janssen Research & Development, Raritan, NJ, USA., Parasrampuria DA; Janssen Research & Development, Spring House, PA, USA., Girgis S; Janssen Research & Development, Spring House, PA, USA., Mason GE; Janssen Research & Development, Spring House, PA, USA., Knoblauch RE; Janssen Research & Development, Spring House, PA, USA., Stone N; Janssen Research & Development, Spring House, PA, USA., Infante JR; Janssen Research & Development, Spring House, PA, USA., Gottardis MM; Janssen Research & Development, Spring House, PA, USA., Fong L; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2022 Feb; Vol. 25 (2), pp. 219-228. Date of Electronic Publication: 2021 Jul 13.
DOI: 10.1038/s41391-021-00402-8
Abstrakt: Background: The safety and immunogenicity of JNJ-64041809 (JNJ-809), a live-attenuated, double-deleted Listeria monocytogenes (LADD Lm)-based immunotherapy targeting 4 relevant prostate cancer antigens, was evaluated in a phase 1 study in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods: Men with progressive mCRPC who had received ≥2 prior approved therapies were enrolled. Primary study objectives were to determine the recommended phase 2 dose (RP2D) and to evaluate the safety and immunogenicity of JNJ-809.
Results: A total of 26 patients received JNJ-809 (1 × 10 8 CFU (n = 6); 1 × 10 9 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 10 9 CFU was selected as the RP2D. The most common adverse events (AEs) reported were chills (92%), pyrexia (81%), and fatigue (62%). The most frequent grade ≥3 AEs were lymphopenia (27%) and hypertension (23%). Serious AEs were reported in 27% of patients including 1 patient with grade 3 intestinal obstruction. JNJ-809 transiently induced peripheral cytokines, including interferon-γ, interleukin-10, and tumor necrosis factor-α. Of the 7 patients evaluable for T cell responses at the 1 × 10 9 CFU dose, evidence of post-treatment antigenic responses were observed in 6 to the Listeria antigen listeriolysin O and in 5 to ≥1 of the 4 encoded tumor antigens. Best overall response was stable disease in 13/25 response-evaluable patients. The study was terminated early as data collected were considered sufficient to evaluate safety and immunogenicity.
Conclusions: JNJ-809 has manageable safety consistent with other LADD Lm-based therapies. Limited antigen-specific immune responses were observed, which did not translate into objective clinical responses.
(© 2021. The Author(s).)
Databáze: MEDLINE
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