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

• ClinicalTrials.gov Identifier: NCT03371381
• Recruitment Status: Terminated
• First Posted: December 13, 2017
• Results First Posted: December 11, 2019
• Last Update Posted: December 11, 2019
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

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 (Clinical Trial)
• 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: January 2, 2018
• Actual Primary Completion Date: October 9, 2018
• Actual Study Completion Date: October 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 Name: 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 [ 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.

Secondary Outcome Measures :

1. Phase 1b: Duration of Objective Response (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 6.8 months ]
   Nivolumab serum concentrations were reported.
8. Phase 1b: Number of Participants With Anti-nivolumab Antibodies [ Time Frame: Up to 6.8 months ]
   Number of participants with antibodies to nivolumab were reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21287

United States, Tennessee

Tennessee Oncology, PLLC

Nashville, Tennessee, United States, 37201

United States, Washington

Medical Oncology Associates, PS

Spokane, Washington, United States, 99208-1129

Belgium

AZ Maria Middelares

Gent, Belgium, 9000

Spain

Hosp. Univ. Quiron Dexeus

Barcelona, Spain, 08028

Hosp. Gral. Univ. de Elche

Elche, Spain, 03203

Complejo Hospitalario de Jaen

Jaén, Spain, 23007

Hosp. Regional Univ. de Malaga

Málaga, Spain, 29010

Hosp. Son Llatzer

Palma de Mallorca, Spain, 07198

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)

Documents provided by Janssen Research & Development, LLC:

Study Protocol and Statistical Analysis Plan  [PDF] January 4, 2018

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03371381
• Other Study ID Numbers: CR108232; 2016-002543-41 ( EudraCT Number ); 64041757LUC2002 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: December 13, 2017
• Results First Posted: December 11, 2019
• Last Update Posted: December 11, 2019
• Last Verified: November 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; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action