PMID- 34589981 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220427 IS - 2666-3643 (Electronic) IS - 2666-3643 (Linking) VI - 2 IP - 2 DP - 2021 Feb TI - JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes-Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies. PG - 100103 LID - 10.1016/j.jtocrr.2020.100103 [doi] LID - 100103 AB - INTRODUCTION: JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted Listeria monocytogenes-based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2). METHODS: Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 x 10(8) or 1 x 10(9) colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 x 10(9) CFU) plus intravenous nivolumab 240 mg (NCT03371381). Study objectives included the assessment of immunogenicity, safety, and efficacy. RESULTS: In the monotherapy study, 18 patients (median age 63.5 y; women 61%) were treated with JNJ-757 (1 x 10(8) or 1 x 10(9) CFU) with a median duration of 1.4 months (range: 0-29). The most common adverse events (AEs) were pyrexia (72%) and chills (61%), which were usually mild and resolved within 48 hours. Peripheral proinflammatory cytokines and lymphocyte activation were induced posttreatment with transient mesothelin-specific T-cell responses in 10 of 13 biomarker-evaluable patients. With monotherapy, four of 18 response-evaluable patients had stable disease of 16 or more weeks, including one patient with a reduction in target lesions. In the combination study, 12 patients were enrolled (median age 63.5 y; women 33%). The most common AEs with combination therapy were pyrexia (67%) and chills (58%); six patients had grade 3 AEs or greater, including two cases of treatment-related fatal pneumonitis. The best overall response for the combination was stable disease in four of nine response-evaluable patients. CONCLUSIONS: As monotherapy, JNJ-757 was immunogenic and tolerable, with mild infusion-related fever and chills. The limited efficacy of JNJ-757, alone or with nivolumab, did not warrant further investigation of the combination. CI - (c) 2020 The Authors. FAU - Brahmer, Julie R AU - Brahmer JR AD - Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. FAU - Johnson, Melissa L AU - Johnson ML AD - Lung Cancer Research and Drug Development, Sarah Cannon Research Institute, Nashville, Tennessee. FAU - Cobo, Manuel AU - Cobo M AD - Unidad de Gestion Clinica Intercentros de Oncologia Medica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigacion Biomedica de Malaga, Malaga, Spain. FAU - Viteri, Santiago AU - Viteri S AD - Dr. Rosell Oncology Institute, Dexeus University Hospital, Quironsalud Group, Barcelona, Spain. FAU - Sarto, Juan Coves AU - Sarto JC AD - Department of Medical Oncology, Hospital Son Llatzer, Palma de Mallorca, Spain. FAU - Sukari, Ammar AU - Sukari A AD - Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. FAU - Awad, Mark M AU - Awad MM AD - Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts. FAU - Salgia, Ravi AU - Salgia R AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California. FAU - Papadimitrakopoulou, Vali A AU - Papadimitrakopoulou VA AD - Department of Medical Oncology, The University of Texas MD Anderson, Houston, Texas. FAU - Rajan, Arun AU - Rajan A AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. FAU - Bandyopadhyay, Nibedita AU - Bandyopadhyay N AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Allred, Alicia J AU - Allred AJ AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Wade, Mark AU - Wade M AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Mason, Gary E AU - Mason GE AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Zudaire, Enrique AU - Zudaire E AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Knoblauch, Roland E AU - Knoblauch RE AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Stone, Nicole AU - Stone N AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Lorenzi, Matthew V AU - Lorenzi MV AD - Janssen Research and Development, Spring House, Pennsylvania. FAU - Hassan, Raffit AU - Hassan R AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. LA - eng PT - Journal Article DEP - 20201005 PL - United States TA - JTO Clin Res Rep JT - JTO clinical and research reports JID - 101769967 PMC - PMC8474274 OTO - NOTNLM OT - JNJ-757 OT - LADD Lm OT - Mesothelin OT - Non-small cell lung cancer OT - Vaccine EDAT- 2021/10/01 06:00 MHDA- 2021/10/01 06:01 PMCR- 2020/10/05 CRDT- 2021/09/30 07:22 PHST- 2020/08/04 00:00 [received] PHST- 2020/09/22 00:00 [revised] PHST- 2020/09/23 00:00 [accepted] PHST- 2021/09/30 07:22 [entrez] PHST- 2021/10/01 06:00 [pubmed] PHST- 2021/10/01 06:01 [medline] PHST- 2020/10/05 00:00 [pmc-release] AID - S2666-3643(20)30149-1 [pii] AID - 100103 [pii] AID - 10.1016/j.jtocrr.2020.100103 [doi] PST - epublish SO - JTO Clin Res Rep. 2020 Oct 5;2(2):100103. doi: 10.1016/j.jtocrr.2020.100103. eCollection 2021 Feb.