Clinical Trials /

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

NCT02592967

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Safety & Immunogenicity of JNJ-64041757, Live-attenuated Double-<span class="go-doc-concept go-doc-keyword">deleted</span> Listeria Immunotherapy, in Subjects With Non Small Cell Lung Cancer

Title

  • Brief Title: Safety & Immunogenicity of JNJ-64041757, Live-attenuated Double-deleted Listeria Immunotherapy, in Subjects With Non Small Cell Lung Cancer
  • Official Title: An Open Label Phase 1 Study of Safety and Immunogenicity of JNJ-64041757, A Live Attenuated Listeria Monocytogenes Immunotherapy, in Subjects With Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02592967

    ORG ID: CR107667

    NCI ID: 64041757LUC1001

    Trial Conditions

    Carcinoma, Non-Small-Cell Lung

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Cohort 1A and 1B Experimental JNJ-64041757 will be administered intravenously (IV) once every 21 days.
    Cohort 2A and 2B Experimental JNJ-64041757 will be administered intravenously (IV) once every 21 days.

    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
    intravenous (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 Food and Drug Administration (FDA)-approved systemic
    therapy, of which one therapy has to be a platinum-containing regimen OR failed 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 equal (>=) 50% of tumor cells with
    intensity of at least 2+ on archived tumor material; 2) Primary tumor or metastatic
    lesion(s) amenable to tumor core biopsies

    - Documented tumor progression based on computed tomography (CT) imaging

    - 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 any time prior to first dose).

    Exclusion Criteria:

    - Previously documented or current brain metastases

    - 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 only allergic to one of these antibiotics are allowed to enroll

    - Concurrent treatment with 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

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

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

    Part 2: Antigen-specific T-cell Response

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

    Secondary Outcome Measures

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

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

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

    Trial Keywords

    Carcinoma, Non-Small-Cell Lung

    JNJ-64041757

    Listeria monocytogenes