Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer
Charles G. Drake, Russell K. Pachynski, Sumit K. Subudhi, Douglas G. McNeel, Emmanuel S. Antonarakis, Todd M. Bauer, Peter Lauer, Dirk G. Brockstedt, Daniel Patricia, Mark Wade, Enrique Zudaire, Nibedita Bandyopadhyay, Dolly A. Parasrampuria, Suzette Girgis, Gary Mason, Roland E. Knoblauch, Nicole L. Stone, Jeffrey R. Infante, Marco M. Gottardis, Lawrence Fong
Abstract
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). 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.