JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes–Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies

JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes–Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies

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). Patients with stage IIIB/IV NSCLC who ha...

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Published in:JTO clinical and research reports 2021-02, Vol.2 (2), p.100103-100103, Article 100103
Main Authors: Brahmer, Julie R., Johnson, Melissa L., Cobo, Manuel, Viteri, Santiago, Sarto, Juan Coves, Sukari, Ammar, Awad, Mark M., Salgia, Ravi, Papadimitrakopoulou, Vali A., Rajan, Arun, Bandyopadhyay, Nibedita, Allred, Alicia J., Wade, Mark, Mason, Gary E., Zudaire, Enrique, Knoblauch, Roland E., Stone, Nicole, Lorenzi, Matthew V., Hassan, Raffit
Format: Article
Language:eng
Subjects:
JNJ-757
LADD Lm
Mesothelin
Non–small cell lung cancer
Original
Vaccine
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Summary: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). 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. 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. 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.
ISSN:2666-3643
2666-3643