Back to Search
Start Over
Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer.
- Source :
-
Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2022 Feb; Vol. 25 (2), pp. 219-228. Date of Electronic Publication: 2021 Jul 13. - Publication Year :
- 2022
-
Abstract
- 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).<br />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.<br />Results: A total of 26 patients received JNJ-809 (1 × 10 <superscript>8</superscript> CFU (n = 6); 1 × 10 <superscript>9</superscript> CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 10 <superscript>9</superscript> 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 <superscript>9</superscript> 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.<br />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.<br /> (© 2021. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1476-5608
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Prostate cancer and prostatic diseases
- Publication Type :
- Academic Journal
- Accession number :
- 34257408
- Full Text :
- https://doi.org/10.1038/s41391-021-00402-8