Clinical trial NCT02592967: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Carcinoma, Non-Small-Cell Lung
JNJ-64041757
Listeria monocytogenes
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Part 1: Incidence of Dose-limiting toxicity (DLT)
timeFrame: First 21 days after the first infusion
measure: Part 2: Antigen-specific T-cell Response
timeFrame: up to 1 year
measure: Part 1 and Part 2: Incidence of Adverse Events (AEs)
timeFrame: From signing of informed consent form to 30 days after last dose of study drug
Secondary outcomes:
measure: Part 1 and Part 2: Objective Response Rate (ORR)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Progression-free Survival (PFS)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Blood Culture Assessment of JNJ-64041757
timeFrame: Periodically during treatment and up to one year after End of Treatment (EOT) visit
measure: Part 1 and Part 2: Shedding Profile of JNJ-64041757 From Cultured Samples of Feces, Urine, and Saliva
timeFrame: During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose)
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.