TY - JOUR
T1 - Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer
AU - Drake, Charles G.
AU - Pachynski, Russell K.
AU - Subudhi, Sumit K.
AU - McNeel, Douglas G.
AU - Antonarakis, Emmanuel S.
AU - Bauer, Todd M.
AU - Lauer, Peter
AU - Brockstedt, Dirk
AU - Patricia, Daniel
AU - Wade, Mark
AU - Zudaire, Enrique
AU - Bandyopadhyay, Nibedita
AU - Parasrampuria, Dolly A.
AU - Girgis, Suzette
AU - Mason, Gary E.
AU - Knoblauch, Roland E.
AU - Stone, Nicole
AU - Infante, Jeffrey R.
AU - Gottardis, Marco M.
AU - Fong, Lawrence
N1 - Funding Information:
Acknowledgements The authors thank the study participants, without whom this study would never have been accomplished and the investigators for their participation in the studies that provided these data. Medical writing was provided by Tracy T. Cao, PhD (Janssen Global Services, LLC) and funded by Janssen Global Services, LLC.
Funding Information:
Funding and role of sponsor This study was funded by Janssen Research & Development, LLC. The sponsor was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - 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 × 108 CFU (n = 6); 1 × 109 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 109 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 × 109 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.
AB - 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 × 108 CFU (n = 6); 1 × 109 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 109 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 × 109 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.
UR - http://www.scopus.com/inward/record.url?scp=85111128848&partnerID=8YFLogxK
U2 - 10.1038/s41391-021-00402-8
DO - 10.1038/s41391-021-00402-8
M3 - Article
C2 - 34257408
AN - SCOPUS:85111128848
SN - 1365-7852
VL - 25
SP - 219
EP - 228
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 2
ER -