TY - JOUR
T1 - JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes–Based Immunotherapy in Patients With NSCLC
T2 - Results From Two Phase 1 Studies
AU - Brahmer, Julie R.
AU - Johnson, Melissa L.
AU - Cobo, Manuel
AU - Viteri, Santiago
AU - Sarto, Juan Coves
AU - Sukari, Ammar
AU - Awad, Mark M.
AU - Salgia, Ravi
AU - Papadimitrakopoulou, Vali A.
AU - Rajan, Arun
AU - Bandyopadhyay, Nibedita
AU - Allred, Alicia J.
AU - Wade, Mark
AU - Mason, Gary E.
AU - Zudaire, Enrique
AU - Knoblauch, Roland E.
AU - Stone, Nicole
AU - Lorenzi, Matthew V.
AU - Hassan, Raffit
N1 - Funding Information:
Disclosure: Dr. Brahmer reports being in a consulting or advisory role for Bristol-Myers Squibb, Eli Lilly, Celgene, Syndax, Janssen Oncology, Merck, Amgen, and Genentech; receiving travel and accommodation expense assistance from Bristol-Myers Squibb and Merck; receiving other forms of assistance from Bristol-Myers Squibb and Merck; and receiving research funding for her institution from Bristol-Myers Squibb, Merck, AstraZeneca, Incyte, Janssen Oncology, and Spectrum Pharmaceuticals. Dr. Johnson reports being in a consulting or advisory role for Otsuka and Astellas Pharma for an immediate family member; reports being in a consulting or advisory role for Achilles Therapeutics, Arcus Biosciences, AstraZeneca, Atreca, Boehringer Ingelheim, Calithera Biosciences, EMD Serono, Genentech, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Incyte, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Ribon Therapeutics, and Sanofi-Aventis; and receiving research funding for her institution from AbbVie, Acerta Pharma, Adaptimmune, Amgen, AstraZeneca, Apexigen, Array BioPharma, Atreca, BeiGene, BerGenBio, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dynavax Technologies, EMD Serono, Foundation Medicine, Genentech, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Eli Lilly, Loxo Oncology, Lycera, Neovia Oncology, Merck, Novartis, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi-Aventis, Seven and Eight Biopharmaceuticals, Shattuck Labs, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, University of Michigan, and WindMIL Therapeutics. Dr. Viteri reports being in a consulting or advisory role for Roche and Bristol-Myers Squibb; receiving travel accommodation and expenses from Merck Serono, Roche, and OSE Pharma; was a member of speakers bureau for Roche and Bristol-Myers Squibb; and receiving research funding from OSE Pharma, Boehringer Ingelheim, Novocure, Merck Serono, Roche, Exelixis, Takeda, and IO Biotech. Dr. Sukari reports being in a consulting or advisory role for Eisai and Bayer Pharmaceuticals; participating in speakers bureau for Merck and Eisai; and receiving research funding from Eisai. Dr. Awad reports being in a consulting or advisory role for Genentech, Merck, Pfizer, Boehringer Ingelheim, AbbVie, AstraZeneca/MedImmune, Clovis Oncology, Nektar, Bristol-Myers Squibb, ARIAD Pharmaceuticals, Foundation Medicine, Syndax, Novartis, Blueprint Medicines, and Maverick Therapeutics; receiving research funding from Bristol-Myers Squibb; and receiving research funding for his institution from Genentech/Roche, Eli Lilly, AstraZeneca, and Bristol-Myers Squibb. Dr. Papadimitrakopoulou is currently an employee of Pfizer, Inc. and reports being in a consulting or advisory role for Clovis Oncology, Genentech, Merck, Biothera, Eli Lilly, Janssen, AstraZeneca, ARIAD Pharmaceuticals, Nektar, Loxo Oncology, Araxes Pharma, AbbVie, Bristol-Myers Squibb, Exelixis, Pfizer, Novartis, Takeda Pharmaceuticals, TRM Oncology, Tesaro, Arrys Therapeutics, Gritstone Oncology, Leeds Biolabs, Bolt Biotherapeutics, and G2 innovation; receiving funding for travel and accommodation expenses from AstraZeneca and Roche; receiving honoraria and other assistance from Roche; and receiving research funding for her institution from Merck, Novartis, Celgene, Clovis Oncology, Bayer, Bristol-Myers Squibb, AstraZeneca, Pfizer, Janssen Oncology, ACEA Biosciences, Nektar, Roche, Eli Lilly, Checkmate Pharmaceuticals, Incyte, and Guardant Health. Dr. Rajan reports receiving research funding for his institution from Aduro Biotech, Morphotek, TCR2, and Bayer Pharmaceuticals. Dr. Bandyopadhyay, Dr. Allred, Mr. Wade, Dr. Mason, Dr. Zudaire, Dr. Knoblauch, and Dr. Stone report employment, stock, or other ownership in Johnson & Johnson. Dr. Lorenzi reports employment, stock, or other ownership in and also receiving funding for travel and accommodation expenses from Johnson & Johnson. Dr. Hassan reports receiving research funding for his institution from Aduro Biotech, Morphotek, TCR2, and Bayer Pharmaceuticals. The remaining authors declare no conflict of interest.
Funding Information:
Medical writing was provided by Tracy T. Cao, PhD (Janssen Global Services, LLC) and funded by Janssen Global Services, LLC. The Sponsor and its employees were involved in the study design, collection, analysis, and interpretation of data, writing of the report, and in the decision to submit the manuscript for publication. 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. Drs. Brahmer, Johnson, Viteri, Sukari, Awad, Papadimitrakopoulou, and Rajan contributed to study execution, review, and analysis of data of the manuscript. Dr. Cobo contributed to study execution, data support, review, and analysis of data of the manuscript. Coves contributed to the study execution of the manuscript. Drs. Salgia, Allred, Mason, Zudaire, and Knoblauch contributed to study conception and design, study execution, review, and analysis of data of the manuscript. Dr. Bandyopadhyay contributed to study conception and design, study execution, review and analysis of data, and formal analyses of the manuscript. Mr. Wade and Dr. Stone contributed to the review and analysis of data of the manuscript. Dr. Lorenzi and Hasan contributed to the study conception and design of the manuscript. All authors contributed to writing the manuscript, approved the submitted version of the manuscript, and agreed to be accountable for all aspects of the work.
Publisher Copyright:
© 2020 The Authors
PY - 2021/2
Y1 - 2021/2
N2 - 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 × 108 or 1 × 109 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 109 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 × 108 or 1 × 109 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.
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 × 108 or 1 × 109 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 109 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 × 108 or 1 × 109 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.
KW - JNJ-757
KW - LADD Lm
KW - Mesothelin
KW - Non–small cell lung cancer
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85104999234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104999234&partnerID=8YFLogxK
U2 - 10.1016/j.jtocrr.2020.100103
DO - 10.1016/j.jtocrr.2020.100103
M3 - Article
C2 - 34589981
AN - SCOPUS:85104999234
SN - 2666-3643
VL - 2
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 2
M1 - 100103
ER -