JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes–Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies
Julie R. Brahmer, Melissa L. Johnson, Manuel Cobo, Santiago Viteri, J. Coves Sarto, Ammar Sukari, Mark M. Awad, Ravi Salgia, Vali A. Papadimitrakopoulou, Arun Rajan, Nibedita Bandyopadhyay, Alicia J. Allred, Mark Wade, Gary Mason, Enrique Zudaire, Roland E. Knoblauch, Nicole L. Stone, Matthew V. Lorenzi, Raffit Hassan
Abstract
INTRODUCTION: -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: CFU) plus intravenous nivolumab 240 mg (NCT03371381). Study objectives included the assessment of immunogenicity, safety, and efficacy. RESULTS: 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.