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

NCT03371381 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: CR1082322016-002543-4164041757LUC2002
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 10

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.

Conditions

Adenocarcinoma of Lung

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 6.8 Months

Secondary Outcomes (8)

• Phase 1b: Duration of Objective Response (DOR)

  Up to 6.8 months

• Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)

  Up to 6.8 months

• Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)

  Up to 6.8 months

• Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to 6.8 months

• Phase 1b: Number of Participants With Positive Blood Culture

  Up to 6.8 months

Study Arms (2)

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.

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.

Drug: Nivolumab

Interventions

JNJ-64041757 BIOLOGICAL

Participants will receive intravenous (IV) infusions of JNJ-64041757 over approximately 60 minutes during each treatment cycle.

Also known as: JNJ-757

Nivolumab + JNJ-64041757

Nivolumab DRUG

Participants will receive IV infusions of nivolumab over approximately 60 minutes during each treatment cycle.

Nivolumab; Nivolumab + JNJ-64041757

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (10)

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37201, United States

Location

Medical Oncology Associates, PS

Spokane, Washington, 99208-1129, United States

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

Hosp. Univ. Quiron Dexeus

Barcelona, 08028, Spain

Location

Hosp. Gral. Univ. de Elche

Elche, 03203, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hosp Regional Univ de Malaga

Málaga, 29010, Spain

Location

Hosp. Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Hosp. Arnau de Vilanova de Valencia

Valencia, 46015, Spain

Location

MeSH Terms

Conditions

Adenocarcinoma of Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and 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.

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 13, 2017
• Study Start: January 2, 2018
• Primary Completion: October 9, 2018
• Study Completion: October 9, 2018
• Last Updated: February 4, 2025
• Results First Posted: December 11, 2019

Record last verified: 2025-01

Locations

US (3); ES (6); BE (1)