Trial Outcomes & Findings for 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 (NCT NCT03371381)

Last Updated: 2025-02-04

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 6.8 Months

Results posted on

2025-02-04

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Phase 1b: JNJ-64041757+ Nivolumab 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 Study STARTED	12
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: JNJ-64041757+ Nivolumab 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 Study Death	5
Overall Study Study terminated by sponsor	3
Overall Study Other	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Age, Continuous	61.2 years STANDARD_DEVIATION 12.63 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants
Race/Ethnicity, Customized White Non-Hispanic	11 Participants n=5 Participants
Region of Enrollment SPAIN	10 Participants n=5 Participants
Region of Enrollment UNITED STATES	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6.8 Months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Percentage of Participants With Objective Response	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)	10 Participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)	5 Participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: Safety analysis set included participants who received at least 1 administration of any study medication.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	12 Participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

Number of participants with surveillance cultures positive for listeriosis were reported.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Positive Blood Culture	1 Participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Bacterial Shedding	0 Participants

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: 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.

Nivolumab serum concentrations were reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6.8 months

Population: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

Number of participants with antibodies to nivolumab were reported.

Outcome measures

Outcome measures
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 Participants 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.
Phase 1b: Number of Participants With Anti-nivolumab Antibodies	6 Participants

Adverse Events

Phase 1b: JNJ-64041757+ Nivolumab

Serious events: 5 serious events

Other events: 12 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 participants at risk 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.
Gastrointestinal disorders Abdominal Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Intestinal Obstruction	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Non-Cardiac Chest Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Oedema Peripheral	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Back Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Skin and subcutaneous tissue disorders Erythema	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.

Other adverse events

Other adverse events
Measure	Phase 1b: JNJ-64041757+ Nivolumab n=12 participants at risk 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.
Blood and lymphatic system disorders Anaemia	41.7% 5/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Blood and lymphatic system disorders Leukocytosis	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Cardiac disorders Sinus Tachycardia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Cardiac disorders Tachycardia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Endocrine disorders Hypothyroidism	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Abdominal Pain	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Constipation	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Dry Mouth	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Nausea	41.7% 5/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Gastrointestinal disorders Vomiting	25.0% 3/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Asthenia	50.0% 6/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Chills	58.3% 7/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Fatigue	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Non-Cardiac Chest Pain	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
General disorders Pyrexia	66.7% 8/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Hepatobiliary disorders Hepatic Failure	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Infections and infestations Pneumonia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Infections and infestations Respiratory Tract Infection	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Infections and infestations Upper Respiratory Tract Infection	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Investigations Blood Creatinine Increased	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Investigations Body Temperature Increased	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Investigations Weight Decreased	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Metabolism and nutrition disorders Decreased Appetite	33.3% 4/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Metabolism and nutrition disorders Hypomagnesaemia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Metabolism and nutrition disorders Hyponatraemia	25.0% 3/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Back Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Joint Swelling	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Limb Discomfort	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	25.0% 3/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Musculoskeletal and connective tissue disorders Pain in Extremity	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Nervous system disorders Dizziness	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Nervous system disorders Headache	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Nervous system disorders Paraesthesia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Nervous system disorders Tremor	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Psychiatric disorders Insomnia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Renal and urinary disorders Renal Failure	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	41.7% 5/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Skin and subcutaneous tissue disorders Dry Skin	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Skin and subcutaneous tissue disorders Erythema	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Vascular disorders Flushing	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Vascular disorders Hypotension	16.7% 2/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.
Vascular disorders Inferior Vena Caval Occlusion	8.3% 1/12 • Up to 6.8 months Safety analysis set included participants who received at least 1 administration of any study medication.

Additional Information

Executive Medical Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER