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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Adenocarcinoma of Lung
Interventions Biological: JNJ-64041757
Drug: Nivolumab
Enrollment 12
Recruitment Details  
Pre-assignment Details The trial consisted of two parts (Phase 1 b and Phase 2). However, Phase 2 was not conducted due to early termination of the study. All analyses were performed on Phase 1b data.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Period Title: Overall Study
Started 12
Completed 0
Not Completed 12
Reason Not Completed
Death             5
Study terminated by sponsor             3
Other             4
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants
61.2  (12.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
4
  33.3%
Male
8
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Hispanic or Latino
1
   8.3%
Not Hispanic or Latino
11
  91.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
12
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Hispanic or Latino
1
   8.3%
White Non-Hispanic
11
  91.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
SPAIN
10
  83.3%
UNITED STATES
2
  16.7%
1.Primary Outcome
Title Phase 1b: Percentage of Participants With Objective Response
Hide Description 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.
Time Frame Up to 6.8 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Percentage of participants
0
2.Secondary Outcome
Title Phase 1b: Duration of Objective Response (DOR)
Hide Description 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.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent. Overall number of participants analyzed is zero, since none of the participants had objective response.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)
Hide Description 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.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
10
  83.3%
4.Secondary Outcome
Title Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)
Hide Description 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.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
5
  41.7%
5.Secondary Outcome
Title Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide 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. TEAEs are defined as adverse events with onset or worsening on or after date of first dose of study treatment.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included participants who received at least 1 administration of any study medication.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
12
 100.0%
6.Secondary Outcome
Title Phase 1b: Number of Participants With Positive Blood Culture
Hide Description Number of participants with surveillance cultures positive for listeriosis were reported.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
1
   8.3%
7.Secondary Outcome
Title Phase 1b: Number of Participants With Bacterial Shedding
Hide Description 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.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
8.Secondary Outcome
Title Phase 1b: Serum Concentrations of Nivolumab
Hide Description Nivolumab serum concentrations were reported.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of study agent and had one PK blood sample available. Although PK samples were collected, but assays were not run due to no longer development of compound.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Phase 1b: Number of Participants With Anti-nivolumab Antibodies
Hide Description Number of participants with antibodies to nivolumab were reported.
Time Frame Up to 6.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated analysis population consisted of participants who received at least 1 dose of study agent.
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description:
Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
6
  50.0%
Time Frame Up to 6.8 months
Adverse Event Reporting Description Safety analysis set included participants who received at least 1 administration of any study medication.
 
Arm/Group Title Phase 1b: JNJ-64041757+ Nivolumab
Hide Arm/Group Description Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day 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.
All-Cause Mortality
Phase 1b: JNJ-64041757+ Nivolumab
Affected / at Risk (%)
Total   5/12 (41.67%) 
Hide Serious Adverse Events
Phase 1b: JNJ-64041757+ Nivolumab
Affected / at Risk (%)
Total   5/12 (41.67%) 
Gastrointestinal disorders   
Abdominal Pain * 1  1/12 (8.33%) 
Intestinal Obstruction * 1  1/12 (8.33%) 
General disorders   
Non-Cardiac Chest Pain * 1  1/12 (8.33%) 
Oedema Peripheral * 1  1/12 (8.33%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  1/12 (8.33%) 
Back Pain * 1  1/12 (8.33%) 
Musculoskeletal Pain * 1  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  1/12 (8.33%) 
Pneumonitis * 1  2/12 (16.67%) 
Skin and subcutaneous tissue disorders   
Erythema * 1  1/12 (8.33%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Phase 1b: JNJ-64041757+ Nivolumab
Affected / at Risk (%)
Total   12/12 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  5/12 (41.67%) 
Leukocytosis * 1  1/12 (8.33%) 
Cardiac disorders   
Sinus Tachycardia * 1  1/12 (8.33%) 
Tachycardia * 1  1/12 (8.33%) 
Endocrine disorders   
Hypothyroidism * 1  1/12 (8.33%) 
Gastrointestinal disorders   
Abdominal Pain * 1  2/12 (16.67%) 
Constipation * 1  1/12 (8.33%) 
Dry Mouth * 1  1/12 (8.33%) 
Nausea * 1  5/12 (41.67%) 
Vomiting * 1  3/12 (25.00%) 
General disorders   
Asthenia * 1  6/12 (50.00%) 
Chills * 1  7/12 (58.33%) 
Fatigue * 1  2/12 (16.67%) 
Non-Cardiac Chest Pain * 1  2/12 (16.67%) 
Pyrexia * 1  8/12 (66.67%) 
Hepatobiliary disorders   
Hepatic Failure * 1  1/12 (8.33%) 
Infections and infestations   
Nasopharyngitis * 1  1/12 (8.33%) 
Pneumonia * 1  1/12 (8.33%) 
Respiratory Tract Infection * 1  2/12 (16.67%) 
Upper Respiratory Tract Infection * 1  1/12 (8.33%) 
Investigations   
Blood Creatinine Increased * 1  1/12 (8.33%) 
Body Temperature Increased * 1  1/12 (8.33%) 
Weight Decreased * 1  1/12 (8.33%) 
Metabolism and nutrition disorders   
Decreased Appetite * 1  4/12 (33.33%) 
Hypomagnesaemia * 1  1/12 (8.33%) 
Hyponatraemia * 1  3/12 (25.00%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  1/12 (8.33%) 
Back Pain * 1  1/12 (8.33%) 
Joint Swelling * 1  1/12 (8.33%) 
Limb Discomfort * 1  1/12 (8.33%) 
Musculoskeletal Chest Pain * 1  1/12 (8.33%) 
Musculoskeletal Pain * 1  3/12 (25.00%) 
Myalgia * 1  1/12 (8.33%) 
Pain in Extremity * 1  1/12 (8.33%) 
Nervous system disorders   
Dizziness * 1  1/12 (8.33%) 
Headache * 1  1/12 (8.33%) 
Paraesthesia * 1  1/12 (8.33%) 
Tremor * 1  1/12 (8.33%) 
Psychiatric disorders   
Insomnia * 1  1/12 (8.33%) 
Renal and urinary disorders   
Renal Failure * 1  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  2/12 (16.67%) 
Dyspnoea * 1  5/12 (41.67%) 
Haemoptysis * 1  1/12 (8.33%) 
Hypoxia * 1  1/12 (8.33%) 
Pneumonitis * 1  1/12 (8.33%) 
Skin and subcutaneous tissue disorders   
Dry Skin * 1  1/12 (8.33%) 
Erythema * 1  1/12 (8.33%) 
Vascular disorders   
Flushing * 1  1/12 (8.33%) 
Hypotension * 1  2/12 (16.67%) 
Inferior Vena Caval Occlusion * 1  1/12 (8.33%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
Sponsor did not proceed to Randomized phase 2 of study or enroll additional participants in phase 1b as study was stopped early, that resulted in limited evaluation of planned participant-related outcomes, PK, immunogenicity and biomarker analyses.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Executive Medical Director
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03371381    
Other Study ID Numbers: CR108232
2016-002543-41 ( EudraCT Number )
64041757LUC2002 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: November 30, 2017
First Posted: December 13, 2017
Results First Submitted: October 10, 2019
Results First Posted: December 11, 2019
Last Update Posted: December 11, 2019