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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

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ClinicalTrials.gov Identifier: NCT03371381
Recruitment Status : Terminated (Development of JNJ-64041757 in combination with nivolumab discontinued due to lack of clinical benefit observed in the Phase 1b portion of the study)
First Posted : December 13, 2017
Results First Posted : December 11, 2019
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE November 30, 2017
First Posted Date  ICMJE December 13, 2017
Results First Submitted Date  ICMJE October 10, 2019
Results First Posted Date  ICMJE December 11, 2019
Last Update Posted Date December 11, 2019
Actual Study Start Date  ICMJE January 2, 2018
Actual Primary Completion Date October 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2019)
Phase 1b: Percentage of Participants With Objective Response [ Time Frame: Up to 6.8 Months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Percentage of Participants With Objective Response [ Time Frame: Week 8 then every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy (approximately 3 years) ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2019)
  • Phase 1b: Duration of Objective Response (DOR) [ Time Frame: Up to 6.8 months ]
    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.
  • Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression) [ Time Frame: Up to 6.8 months ]
    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.
  • Phase 1b: Number of Participants With Overall Survival (OS) Event (Died) [ Time Frame: Up to 6.8 months ]
    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.
  • Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 6.8 months ]
    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.
  • Phase 1b: Number of Participants With Positive Blood Culture [ Time Frame: Up to 6.8 months ]
    Number of participants with surveillance cultures positive for listeriosis were reported.
  • Phase 1b: Number of Participants With Bacterial Shedding [ Time Frame: Up to 6.8 months ]
    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.
  • Phase 1b: Serum Concentrations of Nivolumab [ Time Frame: Up to 6.8 months ]
    Nivolumab serum concentrations were reported.
  • Phase 1b: Number of Participants With Anti-nivolumab Antibodies [ Time Frame: Up to 6.8 months ]
    Number of participants with antibodies to nivolumab were reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Percentage of Participants With Disease Control (DC) [ Time Frame: Week 8 then every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy (approximately 3 years) ]
    DC is defined as the stable disease (SD) lasting for 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.
  • Duration of Objective Response (DOR) [ Time Frame: Week 8 then every 8 weeks for first year, and then every 12 weeks thereafter until disease progression or subsequent therapy (approximately 3 years) ]
    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).
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 3 years ]
    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).
  • Overall Survival (OS) [ Time Frame: Approximately 3 years ]
    Overall survival is defined as the time from the date of randomization to the date of the participant's death.
  • Number of Participants With Adverse Events [ Time Frame: Approximately 3 years ]
    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.
  • Number of Participants With Positive Blood Culture for JNJ-64041757 [ Time Frame: Predose: Day(D) 1 Cycle (C) 1; D2C1; D15C1; D1C2; D1 of each cycle (28 days) with a disease assessment or as clinically indicated;Before prophylactic antibiotic therapy and 3, 6, 9 and 12 months after last dose of JNJ-64041757 (approximately 3 years) ]
    Number of participants with positive blood culture for JNJ-64041757 will be assessed.
  • Participants Assessment of Bacterial Shedding Samples [ Time Frame: 4 hours post dose JNJ- 64041757, D2 C1, Prior to dosing on D15 C1 and D1 C2; End of Treatment visit (approximately 3 years) ]
    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.
  • Serum Concentrations of Nivolumab [ Time Frame: Prior to dosing, 0.5 hour postdose on D15 C1; prior to dosing: D1 of C3, C8, C12, C18 and C24; end of treatment; 100 days after last dose of study agent (approximately 3 years) ]
    Serum concentration assessment will be performed to characterize the pharmacokinetics (PK) of nivolumab.
  • Number of Participants With Anti-nivolumab Antibodies [ Time Frame: Prior to dosing on D1, Prior to dosing, 0.5 hour postdose on D15 C1, Prior to dosing: D1 C2, D1 C3, 8, 12, 18 and 24; end of treatment; 100 days after last dose of study agent (approximately 3 years) ]
    Number of participants exhibiting anti-nivolumab antibodies for nivolumab will be observed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adenocarcinoma of Lung
Intervention  ICMJE
  • Biological: JNJ-64041757
    Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.
    Other Name: JNJ-757
  • Drug: Nivolumab
    Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: JNJ-64041757
    • Drug: Nivolumab
  • 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.
    Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 21, 2018)
12
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
146
Actual Study Completion Date  ICMJE October 9, 2018
Actual Primary Completion Date October 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03371381
Other Study ID Numbers  ICMJE CR108232
2016-002543-41 ( EudraCT Number )
64041757LUC2002 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP