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

NCT ID: NCT02592967

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-02
• Study Completion Date: 2018-10-22

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).

Detailed Description

This is a first-in-human (FIH), Phase 1, open-label, multicenter and 2-part study in participants with advanced (Stage IIIb) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) (adenocarcinoma). Part 1 of study will be Dose Escalation phase to determine the recommended Phase 2 dose (RP2D) based on safety and pharmacodynamic assessments and Part 2 will be Dose Expansion Phase to evaluate 2 expansion cohorts (Cohort 2A and 2B) after the RP2D for JNJ-64041757 is determined in Part 1. The study will consist of a Screening Period (from signing of informed consent until immediately before the first dose), an open-label Treatment Period (from the first dose of study drug until the End-of-Treatment Visit); and a Post treatment Follow-up Period (after the End-of Treatment Visit until study discontinuation). Dose limiting toxicity (DLT) in part 1, antigen-specific T-cell response in part 2 and incidence of adverse events in both the parts will be primarily evaluated.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1A and 1B

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

Group Type: EXPERIMENTAL

JNJ-64041757 (Cohort 1A and 1B)

Intervention Type: 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 2A and 2B

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

Group Type: EXPERIMENTAL

JNJ-64041757 (Cohort 2A and 2B)

Intervention Type: BIOLOGICAL

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

Interventions

JNJ-64041757 (Cohort 1A and 1B)

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)

Intervention Type: BIOLOGICAL

JNJ-64041757 (Cohort 2A and 2B)

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Duarte, California, United States

Baltimore, Maryland, United States

Bethesda, Maryland, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

St Louis, Missouri, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15365184 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22595054 (View on PubMed)

Other Identifiers

64041757LUC1001

Identifier Type: OTHER

Identifier Source: secondary_id

CR107667

Identifier Type: -

Identifier Source: org_study_id