Safety & Immunogenicity of JNJ-64041757, Live-attenuated Double-deleted Listeria Immunotherapy, in Subjects With Non Small Cell Lung Cancer

NCT02592967 | Terminated Phase 1

• 2 other identifiers: CR10766764041757LUC1001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) of JNJ-64041757 a live attenuated double deleted (LADD) Listeria monocytogenes (bacteria in which two virulence genes, which encode molecules that help cause disease, have been removed) when administered intravenously to participants with advanced (Stage IIIb) or metastatic (Stage IV) NSCLC (adenocarcinoma).

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Carcinoma, Non-Small-Cell Lung; JNJ-64041757; Listeria monocytogenes

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of Dose-limiting toxicity (DLT)

  Percentage of participants who experienced DLT will be evaluated. The DLT dose level is defined as an unacceptable level of toxicity as evidenced by a DLT rate of greater than or equal to (\>=) 33%.

  First 21 days after the first infusion

• Part 2: Antigen-specific T-cell Response

  Biomarker analyses leukapheresis will be performed to evaluate immune responses to the vaccine after an single IV immunization.

  up to 1 year

• Part 1 and Part 2: Incidence of Adverse Events (AEs)

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission of any infectious agent via a medicinal product and medically important. Incidence was defined as the number of participants who experienced an adverse event within their period of participation in this study. Severity of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE).

  From signing of informed consent form to 30 days after last dose of study drug

Secondary Outcomes (5)

• Part 1 and Part 2: Objective Response Rate (ORR)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Duration of Response (DOR)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Progression-free Survival (PFS)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Blood Culture Assessment of JNJ-64041757

  Periodically during treatment and up to one year after End of Treatment (EOT) visit

• Part 1 and Part 2: Shedding Profile of JNJ-64041757 From Cultured Samples of Feces, Urine, and Saliva

  During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose)

Study Arms (2)

Cohort 1A and 1B

EXPERIMENTAL

JNJ-64041757 will be administered intravenously (IV) once every 21 days.

Biological: JNJ-64041757 (Cohort 1A and 1B)

Cohort 2A and 2B

EXPERIMENTAL

JNJ-64041757 will be administered intravenously (IV) once every 21 days.

Biological: JNJ-64041757 (Cohort 2A and 2B)

Interventions

JNJ-64041757 (Cohort 1A and 1B) BIOLOGICAL

JNJ-64041757 will be administered IV at a lower dose in Cohort 1A (1x10\^8 colony forming units \[CFU\] ) and at a higher dose in Cohort 1B (1x10\^9 CFU)

Cohort 1A and 1B

JNJ-64041757 (Cohort 2A and 2B) BIOLOGICAL

JNJ-64041757 will be administered intravenously (IV) once every 21 days at the recommended dose as determined in Cohort 1A or 1B.

Cohort 2A and 2B

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 for Part 1 and Part 2: 1) Histologically or cytologically documented non-small cell lung cancer (NSCLC) - adenocarcinoma; 2) Stage III b or IV disease; 3) Tested for presence of echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement; 4) Received at least 2 prior lines of Food and Drug Administration (FDA)-approved systemic therapy, of which one therapy has to be a platinum-containing regimen OR failed or completed a first-line platinum-containing regimen and refused a second-line regimen despite being informed about the different therapeutic options and their specific clinical benefit by the investigator; the content of this informed consent discussion including the therapeutic options reviewed by the investigator needs to be documented and the subject needs to sign a specific consent form; Disease-related criteria for Cohort 2B only: 1) Mesothelin protein overexpression, defined by immunohistochemistry (IHC) as detection of the protein by greater than or equal (\>=) 50 percent (%) of tumor cells on archived tumor material; 2) Primary tumor or metastatic lesion(s) amenable to tumor core biopsies
• At least 1 measurable tumor lesion per RECIST v1.1 (exception: subjects in Part 1 are not required to present with measurable disease)
• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 to 1
• At least 28 days since the last chemotherapy or immunotherapy prior to the first dose; at least 14 days since the last radiation prior to the first dose (exception: palliative radiotherapy for pain can be used greater than or equal to (\>=) 7 days prior to or after infusion)

You may not qualify if:

• Untreated brain metastases. Subjects must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 28 days prior to first dose of study drug
• History of listeriosis or vaccination with a listeria-based vaccine or prophylactic vaccine (eg, influenza, pneumococcal, diphtheria, tetanus, and pertussis \[dTP/dTAP\]) within 28 days of study treatment
• Known allergy to both penicillin and trimethoprim/sulfamethoxazole. Participants who are allergic to only one of these antibiotics are allowed to enroll
• Concurrent treatment with anti-Tumor necrosis factor alpha (TNF alpha) therapies, systemic corticosteroids (prednisone dose greater than \[\>\]10 mg per day or equivalent) or other immune suppressive drugs within the 2 weeks prior to Screening. Steroids that are topical, inhaled, nasal (spray) or ophthalmic solution are permitted
• Positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (9)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Bethesda, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Related Publications (2)

• Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W, Cook DN, Portnoy DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.

  PMID: 15365184 BACKGROUND

• Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.

  PMID: 22595054 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Janssen Research & Development LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: October 30, 2015
• Study Start: December 2, 2015
• Primary Completion: August 14, 2018
• Study Completion: October 22, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (9)