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

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 × 10(8) or 1 × 10(9) colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 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 × 10(8) or 1 × 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.