2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Preliminary immunogenicity, safety, and efficacy of JNJ-64041757 (JNJ-757) in non-small cell lung cancer (NSCLC): Results from two phase 1 studies.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #416)
J Clin Oncol 37, 2019 (suppl; abstr 9093)
Author(s): Julie R. Brahmer, Melissa Lynne Johnson, Manuel Cobo Dols, Santiago Viteri Ramirez, Juan Coves, Ammar Sukari, Mark M. Awad, Ravi Salgia, Vassiliki Papadimitrakopoulou, Arun Rajan, Alicia Jones Allred, Mark Wade, Gary Mason, Enrique Zudaire, Roland Elmar Knoblauch, Nicole L. Stone, Matthew V. Lorenzi, Raffit Hassan; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Sarah Cannon Research Institute, Nashville, TN; Hospital Regional Universitario de Malaga, Málaga, Spain; Dr Rosell Oncology Institute, Dexeus University Hospital, Quiron Salud Group, Barcelona, Spain; Hospital de Son Llatzèr, Palma De Mallorca, Spain; Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detriot, MI; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Janssen Research & Developemnt, Spring House, PA; Janssen Research & Development, Spring House, PA; Janssen Research & Developemnt, Raritan, NJ; Janssen Research and Development, Spring House, PA; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, Bethesda, MD
Background: The immunogenicity, safety, and efficacy of JNJ-757, a live attenuated, double-deleted Listeria monocytogenes-based immunotherapy expressing human mesothelin (MSLN), were evaluated in patients (pts) with advanced NSCLC (adenocarcinoma) as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2). Methods: Adult pts with Stage IIIB/IV NSCLC who had received prior systemic therapy (including 1 platinum-based chemotherapy, prior PD-1/PD-L1 therapy allowed) were included. Dose-limiting toxicities, adverse events (AEs), tumor response, T cell response, and JNJ-757 bacterial shedding profile were evaluated in pts treated with JNJ-757 (108 or 109 colony forming units [CFU]) alone or JNJ-757 (109 CFU)+nivolumab 240 mg combination therapy until progression. Results: In the monotherapy trial, 18 pts (median age 63.5 years; women 61%) were treated with JNJ-757 108 or 109 CFU with a median duration of 1.4 months (range 0-29). Most common AEs were pyrexia (72%) and chills (61%), which were usually mild and resolved within 48 hours, suggesting transient activation of an innate immune response to JNJ-757. Treatment-related grade ≥3 AEs were infrequent (4 [22%]). Induction of peripheral proinflammatory cytokines and lymphocyte activation was observed post-treatment with transient MSLN-specific T cell responses in 10/13 evaluable pts, consistent with the mechanism of action of JNJ-757. With monotherapy, 4/18 response-evaluable pts had stable disease (SD) ≥16 weeks, including 1 pt with a 53% reduction in target lesions. In the combination therapy study, 12 pts were enrolled (median age 63.5 years; women 33%). The most common AEs were pyrexia (67%) and chills (58%); 6 pts had grade ≥3 AEs including 2 cases of treatment-related fatal pneumonitis. Best overall response for the combination was SD in 4/9 evaluable pts. JNJ-757 in combination with nivolumab suggested increased risk of pneumonitis. Conclusions: As monotherapy, JNJ-757 was tolerable with mild infusion-related fever and chills supporting the initiation of the combination therapy study. However, the risk-benefit profile of JNJ-757+nivolumab, did not support proceeding to phase 2. Clinical trial information: NCT02592967, NCT03371381