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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03371381
• Collaborator: (none)
• Enrollment: 12
• Locations: 10
• Arms: 2
• Actual Duration (Months): 9.2
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of Lung	Biological: JNJ-64041757; Drug: Nivolumab	Phase 1/Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 2, 2018
• Actual Primary Completion Date: Oct 9, 2018
• Actual Study Completion Date: Oct 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab + JNJ-64041757 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.	Biological: JNJ-64041757; Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.; Other Names: JNJ-757 ; Drug: Nivolumab; Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.
Active Comparator: Nivolumab 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.	Drug: Nivolumab; Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.

Outcome Measures

Primary Outcome Measures

1. Phase 1b: Percentage of Participants With Objective Response [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.

Secondary Outcome Measures

1. Phase 1b: Duration of Objective Response (DOR) [Up to 6.8 months]

   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.

2. Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression) [Up to 6.8 months]

   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.

3. Phase 1b: Number of Participants With Overall Survival (OS) Event (Died) [Up to 6.8 months]

   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.

4. Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Up to 6.8 months]

   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.

5. Phase 1b: Number of Participants With Positive Blood Culture [Up to 6.8 months]

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

6. Phase 1b: Number of Participants With Bacterial Shedding [Up to 6.8 months]

   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.

7. Phase 1b: Serum Concentrations of Nivolumab [Up to 6.8 months]

   Nivolumab serum concentrations were reported.

8. Phase 1b: Number of Participants With Anti-nivolumab Antibodies [Up to 6.8 months]

   Number of participants with antibodies to nivolumab were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
2	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37201
3	Medical Oncology Associates, PS	Spokane	Washington	United States	99208-1129
4	AZ Maria Middelares	Gent		Belgium	9000
5	Hosp. Univ. Quiron Dexeus	Barcelona		Spain	08028
6	Hosp. Gral. Univ. de Elche	Elche		Spain	03203
7	Complejo Hospitalario de Jaen	Jaén		Spain	23007
8	Hosp. Regional Univ. de Malaga	Málaga		Spain	29010
9	Hosp. Son Llatzer	Palma de Mallorca		Spain	07198
10	Hosp. Arnau de Vilanova de Valencia	Valencia		Spain	46015

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 4, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03371381
• Other Study ID Numbers: CR108232; 2016-002543-41; 64041757LUC2002
• First Posted: Dec 13, 2017
• Last Update Posted: Dec 11, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma; Adenocarcinoma of Lung; Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	The trial consisted of two parts (Phase 1 b and Phase 2). However, Phase 2 was not conducted due to early termination of the study. All analyses were performed on Phase 1b data.

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Period Title: Overall Study
STARTED	12
COMPLETED	0
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (12.63)
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%
Not Hispanic or Latino	11 91.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	1 8.3%
White Non-Hispanic	11 91.7%
Region of Enrollment (Count of Participants)
SPAIN	10 83.3%
UNITED STATES	2 16.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Number [Percentage of participants]	0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The all treated analysis population consisted of participants who received at least 1 dose of study agent. Overall number of participants analyzed is zero, since none of the participants had objective response.

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	10 83.3%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	5 41.7%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	12 100%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	1 8.3%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	0 0%

8. Secondary Outcome

Title	Phase 1b: Serum Concentrations of Nivolumab
Description	Nivolumab serum concentrations were reported.
Time Frame	Up to 6.8 months

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of study agent and had one PK blood sample available. Although PK samples were collected, but assays were not run due to no longer development of compound.

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	0

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
Measure Participants	12
Count of Participants [Participants]	6 50%

Adverse Events

Time Frame	Up to 6.8 months
Adverse Event Reporting Description	Safety analysis set included participants who received at least 1 administration of any study medication.
Arm/Group Title	Phase 1b: JNJ-64041757+ Nivolumab
Arm/Group Description	Participants received nivolumab 240 milligram (mg) intravenous (IV) infusion followed by JNJ-64041757 (1*10^9 colony-forming units [CFUs]) IV infusion on Day 1 and nivolumab 240 mg IV infusion on Day 15 of each 28-day cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
All Cause Mortality
	Phase 1b: JNJ-64041757+ Nivolumab
	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)
Serious Adverse Events
	Phase 1b: JNJ-64041757+ Nivolumab
	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)
Gastrointestinal disorders
Abdominal Pain	1/12 (8.3%)
Intestinal Obstruction	1/12 (8.3%)
General disorders
Non-Cardiac Chest Pain	1/12 (8.3%)
Oedema Peripheral	1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)
Back Pain	1/12 (8.3%)
Musculoskeletal Pain	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/12 (8.3%)
Pneumonitis	2/12 (16.7%)
Skin and subcutaneous tissue disorders
Erythema	1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Phase 1b: JNJ-64041757+ Nivolumab
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Anaemia	5/12 (41.7%)
Leukocytosis	1/12 (8.3%)
Cardiac disorders
Sinus Tachycardia	1/12 (8.3%)
Tachycardia	1/12 (8.3%)
Endocrine disorders
Hypothyroidism	1/12 (8.3%)
Gastrointestinal disorders
Abdominal Pain	2/12 (16.7%)
Constipation	1/12 (8.3%)
Dry Mouth	1/12 (8.3%)
Nausea	5/12 (41.7%)
Vomiting	3/12 (25%)
General disorders
Asthenia	6/12 (50%)
Chills	7/12 (58.3%)
Fatigue	2/12 (16.7%)
Non-Cardiac Chest Pain	2/12 (16.7%)
Pyrexia	8/12 (66.7%)
Hepatobiliary disorders
Hepatic Failure	1/12 (8.3%)
Infections and infestations
Nasopharyngitis	1/12 (8.3%)
Pneumonia	1/12 (8.3%)
Respiratory Tract Infection	2/12 (16.7%)
Upper Respiratory Tract Infection	1/12 (8.3%)
Investigations
Blood Creatinine Increased	1/12 (8.3%)
Body Temperature Increased	1/12 (8.3%)
Weight Decreased	1/12 (8.3%)
Metabolism and nutrition disorders
Decreased Appetite	4/12 (33.3%)
Hypomagnesaemia	1/12 (8.3%)
Hyponatraemia	3/12 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)
Back Pain	1/12 (8.3%)
Joint Swelling	1/12 (8.3%)
Limb Discomfort	1/12 (8.3%)
Musculoskeletal Chest Pain	1/12 (8.3%)
Musculoskeletal Pain	3/12 (25%)
Myalgia	1/12 (8.3%)
Pain in Extremity	1/12 (8.3%)
Nervous system disorders
Dizziness	1/12 (8.3%)
Headache	1/12 (8.3%)
Paraesthesia	1/12 (8.3%)
Tremor	1/12 (8.3%)
Psychiatric disorders
Insomnia	1/12 (8.3%)
Renal and urinary disorders
Renal Failure	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/12 (16.7%)
Dyspnoea	5/12 (41.7%)
Haemoptysis	1/12 (8.3%)
Hypoxia	1/12 (8.3%)
Pneumonitis	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Dry Skin	1/12 (8.3%)
Erythema	1/12 (8.3%)
Vascular disorders
Flushing	1/12 (8.3%)
Hypotension	2/12 (16.7%)
Inferior Vena Caval Occlusion	1/12 (8.3%)

Limitations/Caveats

Sponsor did not proceed to Randomized phase 2 of study or enroll additional participants in phase 1b as study was stopped early, that resulted in limited evaluation of planned participant-related outcomes, PK, immunogenicity and biomarker analyses.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.