PMID- 34257408 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20230421 IS - 1476-5608 (Electronic) IS - 1365-7852 (Print) IS - 1365-7852 (Linking) VI - 25 IP - 2 DP - 2022 Feb TI - Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer. PG - 219-228 LID - 10.1038/s41391-021-00402-8 [doi] 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 x 10(8) CFU (n = 6); 1 x 10(9) CFU (n = 20)). No dose-limiting toxicities were reported, and 1 x 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-gamma, interleukin-10, and tumor necrosis factor-alpha. Of the 7 patients evaluable for T cell responses at the 1 x 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. CI - (c) 2021. The Author(s). FAU - Drake, Charles G AU - Drake CG AUID- ORCID: 0000-0001-9610-3677 AD - Columbia University Medical Center, New York, NY, USA. cdrake2@its.jnj.com. AD - Janssen Research & Development, Spring House, PA, USA. cdrake2@its.jnj.com. FAU - Pachynski, Russell K AU - Pachynski RK AD - Washington University of St. Louis, St. Louis, MO, USA. FAU - Subudhi, Sumit K AU - Subudhi SK AUID- ORCID: 0000-0001-5208-7732 AD - The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - McNeel, Douglas G AU - McNeel DG AUID- ORCID: 0000-0003-1471-6723 AD - University of Wisconsin Carbone Cancer Center, Madison, WI, USA. FAU - Antonarakis, Emmanuel S AU - Antonarakis ES AD - Johns Hopkins Kimmel Medical Institute, Baltimore, MD, USA. FAU - Bauer, Todd M AU - Bauer TM AD - Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA. FAU - Lauer, Peter AU - Lauer P AD - Aduro Biotech, Berkeley, CA, USA. FAU - Brockstedt, Dirk AU - Brockstedt D AD - Aduro Biotech, Berkeley, CA, USA. FAU - Patricia, Daniel AU - Patricia D AD - Janssen Research & Development, Spring House, PA, USA. FAU - Wade, Mark AU - Wade M AD - Janssen Research & Development, Spring House, PA, USA. FAU - Zudaire, Enrique AU - Zudaire E AD - Janssen Research & Development, Spring House, PA, USA. FAU - Bandyopadhyay, Nibedita AU - Bandyopadhyay N AD - Janssen Research & Development, Raritan, NJ, USA. FAU - Parasrampuria, Dolly A AU - Parasrampuria DA AD - Janssen Research & Development, Spring House, PA, USA. FAU - Girgis, Suzette AU - Girgis S AD - Janssen Research & Development, Spring House, PA, USA. FAU - Mason, Gary E AU - Mason GE AD - Janssen Research & Development, Spring House, PA, USA. FAU - Knoblauch, Roland E AU - Knoblauch RE AD - Janssen Research & Development, Spring House, PA, USA. FAU - Stone, Nicole AU - Stone N AD - Janssen Research & Development, Spring House, PA, USA. FAU - Infante, Jeffrey R AU - Infante JR AD - Janssen Research & Development, Spring House, PA, USA. FAU - Gottardis, Marco M AU - Gottardis MM AD - Janssen Research & Development, Spring House, PA, USA. FAU - Fong, Lawrence AU - Fong L AUID- ORCID: 0000-0002-6428-428X AD - UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210713 PL - England TA - Prostate Cancer Prostatic Dis JT - Prostate cancer and prostatic diseases JID - 9815755 SB - IM MH - Humans MH - Immunotherapy/adverse effects MH - *Listeria monocytogenes/genetics MH - Male MH - *Prostatic Neoplasms, Castration-Resistant/pathology PMC - PMC9184270 COIS- C.G.D. is a current employee of Janssen R&D and reports prior consulting or advisory role for AstraZeneca/MedImmune, Bristol-Myers Squibb, Compugen, Roche/Genentech, Janssen Oncology, Pfizer, Tizona Therapeutics, Inc., Potenza Therapeutics, Merck, Rubius, and Pierre Fabre; travel, accommodation, expenses from Roche/Genentech, AACR, ASCO, Merck Sharp & Dohme, and Pfizer; patents licensed from Johns Hopkins to Bristol-Myers Squibb; stock and other ownership interests in Compugen, Tizona Therapeutics, Inc., Harpoon Therapeutics, and Kleo Pharmaceuticals; and research funding to Johns Hopkins from Bristol-Myers Squibb. R.K.P. reports consulting or advisory role for EMD Serono, Bristol-Myers Squibb, Pfizer/EMD Serono, Sanofi, Jounce Therapeutics, Dendreon, Bayer, and Genomic Health; speakers' bureau for Dendreon, Merck, Genentech/Roche, AstraZeneca, Sanofi, and Genomic Health; travel, accommodations, expenses from Genentech/Roche, DAVA Oncology; and research funding from Janssen Oncology. S.K.S. reports consulting or advisory role for Amgen, Apricity Health, AstraZeneca, Bayer, Bristol-Myers Squibb, Dava Oncology, Dendreon, Exelixis, Janssen Oncology, and Polaris; travel, accommodations, expenses from AstraZeneca, Bristol-Myers Squibb, Dava Oncology, Dendreon, Parker Institute of Cancer Immunotherapy, and Society for Immunotherapy of Cancer; stock or other ownership in Apricity Health; honoraria from AstraZeneca, Bristol-Myers Squibb, Dava Oncology, Dendreon, Parker Institute of Cancer Immunotherapy, and Society for Immunotherapy of Cancer; and research funding to his institution from AstraZeneca, Bristol-Myers Squibb, and Janssen Oncology. D.G.M. reports consulting or advisory role for Madison Vaccines, Inc.; leadership role for Madison Vaccines, Inc.; travel, accommodations, expenses from Madison Vaccines, Inc., patents licensed from his institution to Madison Vaccines, Inc.; stock and other ownership interests in Madison Vaccines, Inc.; research funding to his institution from Madison Vaccines, Inc. and from Janssen, Bristol-Myers Squibb, Pfizer, Merck, and Novartis. E.S.A. reports consulting or advisory role for Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma, Merck, AstraZeneca, and Clovis Oncology; travel, accommodations, expenses from Sanofi, Dendreon, and Medivation; co-inventor of a biomarker technology that has been licensed to Qiagen; honoraria from Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma, Merck, AstraZeneca, and Clovis Oncology; research funding to his institution from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, and Constellation Pharmaceuticals. T.M.B. reports employment with Tennessee Oncology; consulting or advisory role for Guardant Health, Loxo, Pfizer, and Exelixis; consulting or advisory role for his institution for Ignyta, Moderna Therapeutics, and Pfizer; speakers' bureau for Bayer; travel, accommodations, expenses from Astellas Pharma, AstraZeneca, Celgene, Clovis Oncology, EMD Serono, Genentech, Lilly, Merck, Novartis, Pharmacyclics, and Sysmex; research funding to his institution from Daiichi Sankyo, Medpacto, Inc., Incyte, Mirati Therapeutics, MedImmune, AbbVie, AstraZeneca, Leap Therapeutics, MabVax, Stemline Therapeutics, Merck, Lilly, GlaxoSmithKline, Novartis, Pfizer, Genentech/Roche, Deciphera, Merrimack, Immunogen, Millennium, Ignyta, Calithera Biosciences, Kolltan Pharmaceuticals, Principa Biopharma, Peleton, Immunocore, Roche, Aileron Therapeutics, Bristol-Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma, Five Prime Therapeutics, Jacobio, Top Alliance BioScience, Loxo, Janssen, Clovis Oncology, Takeda, Karyopharm Therapeutics, Onyx, Phosplatin Therapeutics, Foundation Medicine, and ARMO BioSciences. P.L. and Dr. D.B. report former employment with Aduro Biotech. D.P., M.W., E.Z., N.B., D.A.P., S.G., G.E.M., R.E.K., N.S., J.R.I., and M.M.G. report employment with Janssen R&D and stock or other ownership in Johnson & Johnson. L.F. reports consulting or advisory role for Atreca, Nutcracker Therapeutics, Inc., Bolt Biotherapeutics, BioAtla, and TeneoBio and research funding to his institution from Bristol-Myers Squibb, AbbVie, Roche/Genentech, Janssen Oncology, Merck, Bavarian Nordic, and Dendreon. EDAT- 2021/07/15 06:00 MHDA- 2022/06/14 06:00 PMCR- 2021/07/13 CRDT- 2021/07/14 06:56 PHST- 2020/12/14 00:00 [received] PHST- 2021/05/27 00:00 [accepted] PHST- 2021/05/06 00:00 [revised] PHST- 2021/07/15 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2021/07/14 06:56 [entrez] PHST- 2021/07/13 00:00 [pmc-release] AID - 10.1038/s41391-021-00402-8 [pii] AID - 402 [pii] AID - 10.1038/s41391-021-00402-8 [doi] PST - ppublish SO - Prostate Cancer Prostatic Dis. 2022 Feb;25(2):219-228. doi: 10.1038/s41391-021-00402-8. Epub 2021 Jul 13.