Adenocarcinoma of LungPhase 1/2NCT03371381
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
A Phase 1/2 study testing JNJ-64041757 and Nivolumab in people with Adenocarcinoma of Lung, run by Janssen Research & Development, LLC at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of Lung
- What is being tested?
- JNJ-64041757 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 2 Jan 2018to 9 Oct 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Spain6 sites
Hosp. Univ. Quiron Dexeus
Barcelona, 08028
Hosp. Gral. Univ. de Elche
Elche, 03203
Complejo Hospitalario de Jaen
Jaén, 23007
Hosp Regional Univ de Malaga
Málaga, 29010
Hosp. Son Llatzer
Palma de Mallorca, 07198
Hosp. Arnau de Vilanova de Valencia
Valencia, 46015
United States3 sites
Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Tennessee Oncology, PLLC
Nashville, Tennessee, 37201
Medical Oncology Associates, PS
Spokane, Washington, 99208-1129
About this study
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
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.
Read the 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.
- Conditions
- Adenocarcinoma of Lung
- Being tested
- JNJ-64041757, Nivolumab
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-64041757Biological
Also called JNJ-757
Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.
NivolumabDrug
Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab + JNJ-64041757 | Experimental | 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. Receives: Biological: JNJ-64041757; Drug: Nivolumab |
| Nivolumab | Active comparator | 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. Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6.8 Months
Secondary outcomes (8)
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.
Measured: Up to 6.8 months
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.
Measured: Up to 6.8 months
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.
Measured: Up to 6.8 months
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.
Measured: Up to 6.8 months
Phase 1b: Number of Participants With Positive Blood Culture
Number of participants with surveillance cultures positive for listeriosis were reported.
Measured: Up to 6.8 months
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.
Measured: Up to 6.8 months
Phase 1b: Serum Concentrations of Nivolumab
Nivolumab serum concentrations were reported.
Measured: Up to 6.8 months
Phase 1b: Number of Participants With Anti-nivolumab Antibodies
Number of participants with antibodies to nivolumab were reported.
Measured: Up to 6.8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2017
- Study start2 Jan 2018
- Primary completion9 Oct 2018
- Study completion9 Oct 2018
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of LungStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03371381
- Sponsor's protocol ID
- CR108232
- Other IDs
- 2016-002543-41, 64041757LUC2002, 2016
- Status last verified
- Jan 2025
- First submitted
- 30 Nov 2017
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03371381
- Acronym / sponsor ID
- CR108232
- Conditions
- Adenocarcinoma of Lung
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Jan 2018 (actual)
- Primary completion
- 9 Oct 2018 (actual)
- Study completion
- 9 Oct 2018 (actual)
- First posted
- 13 Dec 2017 (actual)
- Results
- Posted 11 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + JNJ-64041757 | Experimental | Biological: JNJ-64041757, Drug: NivolumabPhase 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 | Active comparator | Drug: NivolumabPhase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-64041757Also: JNJ-757Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle. | Biological | Nivolumab + JNJ-64041757 |
| NivolumabParticipants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle. | Drug | Nivolumab, Nivolumab + JNJ-64041757 |
Primary outcome
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.
8 secondary outcomes
Phase 1b: Duration of Objective Response (DOR)
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Positive Blood Culture
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Bacterial Shedding
Time frame: Up to 6.8 months
Phase 1b: Serum Concentrations of Nivolumab
Time frame: Up to 6.8 months
Phase 1b: Number of Participants With Anti-nivolumab Antibodies
Time frame: Up to 6.8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing JNJ-64041757 and Nivolumab in people with Adenocarcinoma of Lung, run by Janssen Research & Development, LLC at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain, United States, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b: Percentage of Participants With Objective Response (time frame: Up to 6.8 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.