Clinical Trial Results:
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
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Summary
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EudraCT number |
2016-002543-41 |
Trial protocol |
ES BE |
Global end of trial date |
09 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Oct 2019
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First version publication date |
24 Oct 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
64041757LUC2002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03371381 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen Research & Development, LLC
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Sponsor organisation address |
920 Route 202, Raritan, United States, NJ 08869
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Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Oct 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Oct 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this study was to evaluate whether the efficacy of JNJ-64041757 combined with nivolumab was better than the efficacy of nivolumab monotherapy for the subjects with mesothelin-positive relapsed/refractory Stage IIIB or Stage IV adenocarcinoma of the lung, by PD-L1 level.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety evaluations included monitoring of adverse events, clinical laboratory tests, symptom directed physical examinations, electrocardiograms (ECGs), vital signs, and ECOG performance status.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Mar 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 10
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Country: Number of subjects enrolled |
United States: 2
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Worldwide total number of subjects |
12
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
6
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
A total of 12 subjects were enrolled and treated in Phase 1b. No subject was enrolled in phase 2 of the study. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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JNJ-64041757+Nivolumab | ||||||||||||||
Arm description |
Subjects 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. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
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Other name |
OPDIVO
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received IV infusions of nivolumab 240mg over approximately 60 minutes on Days 1 and 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.
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Investigational medicinal product name |
JNJ-64041757
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received intravenous (IV) infusions of JNJ-64041757 (1*10^9 CFUs) over approximately 60 minutes on Day 1 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.
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Baseline characteristics reporting groups
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Reporting group title |
JNJ-64041757+Nivolumab
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Reporting group description |
Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
JNJ-64041757+Nivolumab
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Reporting group description |
Subjects 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. | ||
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End point title |
Phase 1b: Percentage of Subjects with Objective Response [1] | ||||||||
End point description |
Objective response rate is defined as the percentage of subjects 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 - the 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. The all treated analysis population consisted of subjects who received at least 1 dose of study agent.
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End point type |
Primary
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End point timeframe |
Up to 6.8 Months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1b: Duration of Objective Response (DOR) | ||||||||
End point description |
DOR- 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). Subjects 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). Subjects 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. The all treated analysis population consisted of subjects who received at least 1 dose of study agent.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| Notes [2] - Overall number of subjects analyzed is zero, since none of the subjects had objective response. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1b: Number of Subjects with Progression-free Survival (PFS) | ||||||||
End point description |
PFS - time from date of randomization until date of first documented evidence of PD (or relapse for subjects 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). Subjects 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). Subjects 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. The all treated analysis population consisted of subjects who received at least 1 dose of study agent. Number of subjects with PFS event were reported.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1b: Number of Subjects with Overall Survival (OS) | ||||||||
End point description |
Overall Survival was defined as the duration from the date of randomization to the date of subject's death due to subjects with OS event (died) were reported.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1b: Number of Subjects with Treatment Emergent Adverse Events (TEAEs) | ||||||
End point description |
An adverse event is any untoward medical event that occurs in a subject 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. Safety analysis set included subjects who received at least 1 administration of any study medication.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||
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End point title |
Phase 1b: Number of Subjects With Positive Blood Culture | ||||||
End point description |
Number of subjects with surveillance cultures positive for listeriosis were reported. The all treated analysis population consisted of subjects who received at least 1 dose of study agent.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||
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End point title |
Phase 1b: Number of Subjects with Bacterial Shedding | ||||||
End point description |
Number of subjects with bacterial shedding were reported. The shedding of JNJ-64041757 was studied in feces by stool or rectal swab, urine, and saliva. The all treated analysis population consisted of subjects who received at least 1 dose of study agent.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||
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End point title |
Phase 1b: Serum Concentrations of Nivolumab | ||||||||
End point description |
Nivolumab serum concentrations were reported. Pharmacokinetic (PK) population consisted of all subjects who received at least 1 dose of study agent and had one PK blood sample available. Early termination of study limited the evaluation of planned PK analysis.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| Notes [3] - Early termination of study limited the evaluation of planned PK analysis. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1b: Number of Subjects With Anti-nivolumab Antibodies | ||||||
End point description |
Number of subjects with antibodies to nivolumab were reported. The all treated analysis population consisted of subjects who received at least 1 dose of study agent.
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End point type |
Secondary
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End point timeframe |
Up to 6.8 months
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 6.8 months
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Adverse event reporting additional description |
Safety analysis set included subjects who received at least 1 administration of any study medication.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
JNJ-64041757+Nivolumab
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Reporting group description |
Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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02 Jun 2017 |
Protocol Amendment-1 included following changes: Added a phase 1b Run-in phase to assess the safety of the combination of JNJ-64041757 (JNJ-757) with nivolumab, clarified that the phase 2 randomization was limited to subjects with mesothelin-positive status at Screening, changed the stratification for randomization to 3 levels of programmed death receptor ligand-1, modified the assessment schedules for biomarkers, disease evaluation, blood cultures, nivolumab pharmacokinetics, and nivolumab immunogenicity, added measurements of patient-reported outcomes and updated the nivolumab dosing schedule and safety evaluations based on revisions to product labeling for nivolumab. |
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04 Jan 2018 |
Protocol Amendment-2 included following changes: Added mesothelin-positive status as an inclusion criterion for all subjects enrolled (phase 1b and phase 2) at Screening and modifications were made to the assessment schedules for biomarkers, core needle biopsy and to add biomarker measurements. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| Sponsor did not proceed to Randomized phase 2 of study or enroll additional subjects in phase 1b as study was stopped early that resulted in limited evaluation of planned patient-related outcomes, PK, immunogenicity and biomarker analyses. | |||||||
