An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung

An Open-Label Randomized Phase 1b/2 Study of the Efficacy and Safety of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Subjects With Advanced Adenocarcinoma of the Lung

The purpose of this study is to evaluate whether the efficacy of JNJ-757 combined with nivolumab is better than the efficacy of nivolumab monotherapy for participants with mesothelin-positive relapsed/refractory Stage IIIB or Stage IV adenocarcinoma of the lung. The open-label study comprises of two parts i.e. Phase 1b (safety run-in) and Phase 2. Phase1b consists of 1 arm whereas Phase 2 is randomized into 2 groups i.e. Group A and Group B.

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma of Lung
• Intervention / Treatment: Biological: JNJ-64041757; Drug: Nivolumab

Detailed Description

This study evaluates safety and efficacy of JNJ-64041757 with nivolumab. The total study duration will be up to 3 years. It will consist of safety run-in and randomized phase which will comprise of Screening phase(Day(D) -28 to D -1),Treatment Phase,End of Adverse Event Evaluation Period (100 D after last dose of nivolumab)and Post-treatment Follow-up Phase(Every 3 Months). The primary hypothesis is that addition of JNJ-640417577 to nivolumab will result in higher objective response rate compared with nivolumab monotherapy in at least one of programmed death receptor ligand 1 subgroups in participants with relapsed or refractory StageIIIB or StageIV adenocarcinoma of lung. The study procedures include blood culture bacterial shedding assessments, pharmacokinetics, immunogenicity, and biomarkers. Safety will be monitored throughout study.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • AZ Maria Middelares
• Spain
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • Elche, Spain, 03203
    • Hosp. Gral. Univ. de Elche
  • Jaén, Spain, 23007
    • Complejo Hospitalario de Jaén
  • Málaga, Spain, 29010
    • Hosp. Regional Univ. de Malaga
  • Palma de Mallorca, Spain, 07198
    • Hosp. Son Llatzer
  • Valencia, Spain, 46015
    • Hosp. Arnau de Vilanova de Valencia
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37201
      • Tennessee Oncology, PLLC
  • Washington
    • Spokane, Washington, United States, 99208-1129
      • Medical Oncology Associates, PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Disease-related criteria: Histologically documented adenocarcinoma of the lung; Stage IIIB or Stage IV disease; Biopsy material available for central assessment of programmed death receptor ligand 1 (PD-L1) and mesothelin
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Progressive disease during or after platinum-based doublet chemotherapy
• A woman of childbearing potential must have a negative serum or urine pregnancy test within 14 days before the first dose of nivolumab
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• Tumor with activating epidermal growth factor receptor (EGFR) mutation or ALK translocation
• More than 1 prior line of chemotherapy for metastatic disease (Phase 2)
• History of disallowed therapies, as follows: In Phase 1b only: Prior exposure to anti-programmed death receptor-1(PD1), anti programmed death receptor ligand 1 (PD-L1), anti-programmed death receptor ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody within 28 days before the first dose of study agent, In Phase 2 only: Prior exposure to anti-PD1, anti PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody, History of listeriosis or vaccination with a Listeria-based vaccine or prophylactic vaccine within 28 days before the first dose of study agent, Chemotherapy within 28 days before the first dose of study agent, Radiation within 14 days before the first dose of study agent
• History of any other condition that may require the initiation of anti-tumor necrosis factor alpha (TNF alpha) therapies or other immunosuppressant medications during the study
• Active second malignancy within 2 years prior to Cycle 1 Day 1 (Phase 1b) or randomization (Phase 2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + JNJ-64041757; Phase 1b and Phase 2 Group A/Arm 1: Participants will receive separate intravenous (IV) infusions of nivolumab and JNJ-64041757 over approximately 60 minutes during each treatment cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.	Biological: JNJ-64041757; Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.; Other Names: JNJ-757; Drug: Nivolumab; Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.
Active Comparator: Nivolumab; Phase 2 Group B/Arm 2: Participants will receive intravenous (IV) infusions of nivolumab over approximately 60 minutes during each treatment cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.	Drug: Nivolumab; Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Percentage of Participants With Objective Response	Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). RECIST for CR - disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR - greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.	Up to 6.8 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Duration of Objective Response (DOR)	Duration of objective response was defined as the time from initial documentation of a response (CR or PR) to first documented date of disease progression (PD) or death from any cause. RECIST for PD - sum of diameters had increased by >= 20% and >=5 mm from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, there was an overall level of substantial worsening that merits discontinuation of therapy (if target disease is stable disease [SD]/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden must be comparable to increase required for PD of measurable disease. Furthermore, appearance of 1 or more new lesions or unequivocal progression of a non-target lesion.	Up to 6.8 months
Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)	Number of participants with PFS event (progressed or died before progression) were reported. PFS - time from date of randomization until date of first documented evidence of PD (or relapse for participants who experience CR during study) or death from any cause, whichever comes first. RECIST for PD - sum of diameters had increased by >= 20% and >=5 mm from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, there was an overall level of substantial worsening that merits discontinuation of therapy (if target disease is SD/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden must be comparable to increase required for PD of measurable disease. Furthermore, appearance of 1 or more new lesions or unequivocal progression of a non-target lesion.	Up to 6.8 months
Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)	Number of participants with OS event (died) were reported. Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause.	Up to 6.8 months
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as adverse events with onset or worsening on or after date of first dose of study treatment.	Up to 6.8 months
Phase 1b: Number of Participants With Positive Blood Culture	Number of participants with surveillance cultures positive for listeriosis were reported.	Up to 6.8 months
Phase 1b: Number of Participants With Bacterial Shedding	Number of participants with bacterial shedding were reported. The shedding of JNJ-64041757 was studied in feces by stool or rectal swab, urine and saliva.	Up to 6.8 months
Phase 1b: Serum Concentrations of Nivolumab	Nivolumab serum concentrations were reported.	Up to 6.8 months
Phase 1b: Number of Participants With Anti-nivolumab Antibodies	Number of participants with antibodies to nivolumab were reported.	Up to 6.8 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Actual): October 9, 2018
• Study Completion (Actual): October 9, 2018

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2019
• Last Update Submitted That Met QC Criteria: November 23, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CR108232; 2016-002543-41 (EudraCT Number); 64041757LUC2002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No