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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

NCT03371381

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CR108232
  • SECONDARY ID: 2016-002543-41
  • SECONDARY ID: 64041757LUC2002
  • NCT ID: NCT03371381

Conditions

  • Adenocarcinoma of Lung

Interventions

DrugSynonymsArms
JNJ-64041757JNJ-757Nivolumab + JNJ-64041757
NivolumabNivolumab + JNJ-64041757

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + JNJ-64041757ExperimentalPhase 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.
  • Nivolumab
NivolumabActive ComparatorPhase 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.
  • Nivolumab

Eligibility Criteria

        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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Objective Response
Time Frame:Every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy or completion of therapy (approximately 3 years)
Safety Issue:
Description:Objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST); CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm); PR defined as 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.

Secondary Outcome Measures

Measure:Percentage of Participants With Disease Control (DC)
Time Frame:Every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy or completion of therapy (approximately 3 years)
Safety Issue:
Description:DC is defined as the stable disease (SD) lasting for at least 16 weeks, PR or CR. CR or PR according to RECIST Version 1.1. SD defined as less than 30 percent decrease in sum of diameters of all target lesions compared with baseline and less than 20 percent increase compared with nadir, in the absence of new lesions or unequivocal progression of nontarget lesions.
Measure:Duration of Objective Response (DOR)
Time Frame:Every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy or completion of therapy (approximately 3 years)
Safety Issue:
Description:DOR will be assessed only in participants who achieved a CR or PR, and measured from the first documented date of response to the first documented date of disease progression (according to RECIST v1.1) or death from any cause. Progressive Disease (PD) is defined as the sum of the diameters has increased by greater than or equal to 20 percent and greater than or equal to 5 millimeter (mm) from nadir (including baseline if it is the smallest sum).
Measure:Progression-Free Survival (PFS)
Time Frame:Approximately 3 years
Safety Issue:
Description:PFS will be assessed as time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death from any cause, whichever comes first. Progressive Disease (PD) is defined as the sum of the diameters has increased by greater than or equal to 20 percent and greater than or equal to 5 mm from nadir (including baseline if it is the smallest sum).
Measure:Overall Survival (OS)
Time Frame:Approximately 3 years
Safety Issue:
Description:Overall survival is defined as the time from the date of randomization to the date of the participant's death.
Measure:Number of Participants With Adverse Events
Time Frame:Approximately 3 years
Safety Issue:
Description: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.
Measure:Number of Participants With Positive Blood Culture for JNJ-64041757
Time Frame:Approximately 3 years
Safety Issue:
Description:Number of participants with positive blood culture for JNJ-64041757 will be assessed.
Measure:Participants Assessment of Bacterial Shedding Samples
Time Frame:Approximately 3 years
Safety Issue:
Description:The shedding of JNJ-64041757 will be studied in feces by stool or rectal swab, urine, and saliva. Any participant with a positive shedding result will be tested every 2 to 4 days until a negative shedding result.
Measure:Serum Concentrations of Nivolumab
Time Frame:Approximately 3 years
Safety Issue:
Description:Serum concentration assessment will be performed to characterize the pharmacokinetics (PK) of nivolumab.
Measure:Number of Participants With Anti-nivolumab Antibodies
Time Frame:Approximately 3 years
Safety Issue:
Description:Number of participants exhibiting anti-nivolumab antibodies for nivolumab will be observed.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

April 23, 2018