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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

Primary Purpose

Adenocarcinoma of Lung

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JNJ-64041757
Nivolumab
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of Lung

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
  • Tennessee Oncology, PLLC
  • Medical Oncology Associates, PS
  • AZ Maria Middelares
  • Hosp. Univ. Quiron Dexeus
  • Hosp. Gral. Univ. de Elche
  • Complejo Hospitalario de Jaen
  • Hosp. Regional Univ. de Malaga
  • Hosp. Son Llatzer
  • Hosp. Arnau de Vilanova de Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nivolumab + JNJ-64041757

Nivolumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Phase 1b: Number of Participants With Positive Blood Culture
Number of participants with surveillance cultures positive for listeriosis were reported.
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.
Phase 1b: Serum Concentrations of Nivolumab
Nivolumab serum concentrations were reported.
Phase 1b: Number of Participants With Anti-nivolumab Antibodies
Number of participants with antibodies to nivolumab were reported.

Full Information

First Posted
November 30, 2017
Last Updated
November 23, 2019
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03371381
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Development of JNJ-64041757 in combination with nivolumab discontinued due to lack of clinical benefit observed in the Phase 1b portion of the study
Study Start Date
January 2, 2018 (Actual)
Primary Completion Date
October 9, 2018 (Actual)
Study Completion Date
October 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of Lung

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nivolumab + JNJ-64041757
Arm Type
Experimental
Arm Description
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.
Arm Title
Nivolumab
Arm Type
Active Comparator
Arm Description
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 Type
Biological
Intervention Name(s)
JNJ-64041757
Other Intervention Name(s)
JNJ-757
Intervention Description
Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.
Primary Outcome Measure Information:
Title
Phase 1b: Percentage of Participants With Objective Response
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
Secondary Outcome Measure Information:
Title
Phase 1b: Duration of Objective Response (DOR)
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
Title
Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)
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
Title
Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)
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
Title
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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
Title
Phase 1b: Number of Participants With Positive Blood Culture
Description
Number of participants with surveillance cultures positive for listeriosis were reported.
Time Frame
Up to 6.8 months
Title
Phase 1b: Number of Participants With Bacterial Shedding
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
Title
Phase 1b: Serum Concentrations of Nivolumab
Description
Nivolumab serum concentrations were reported.
Time Frame
Up to 6.8 months
Title
Phase 1b: Number of Participants With Anti-nivolumab Antibodies
Description
Number of participants with antibodies to nivolumab were reported.
Time Frame
Up to 6.8 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37201
Country
United States
Facility Name
Medical Oncology Associates, PS
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208-1129
Country
United States
Facility Name
AZ Maria Middelares
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Hosp. Univ. Quiron Dexeus
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
Hosp. Gral. Univ. de Elche
City
Elche
ZIP/Postal Code
03203
Country
Spain
Facility Name
Complejo Hospitalario de Jaen
City
Jaén
ZIP/Postal Code
23007
Country
Spain
Facility Name
Hosp. Regional Univ. de Malaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hosp. Son Llatzer
City
Palma de Mallorca
ZIP/Postal Code
07198
Country
Spain
Facility Name
Hosp. Arnau de Vilanova de Valencia
City
Valencia
ZIP/Postal Code
46015
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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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