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).
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
- ORG STUDY ID:
CR107667
- SECONDARY ID:
64041757LUC1001
- NCT ID:
NCT02592967
Conditions
- Carcinoma, Non-Small-Cell Lung
Interventions
Drug | Synonyms | Arms |
---|
JNJ-64041757 (Cohort 1A and 1B) | | Cohort 1A and 1B |
JNJ-64041757 (Cohort 2A and 2B) | | Cohort 2A and 2B |
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. | - JNJ-64041757 (Cohort 1A and 1B)
|
Cohort 2A and 2B | Experimental | JNJ-64041757 will be administered intravenously (IV) once every 21 days. | - JNJ-64041757 (Cohort 2A and 2B)
|
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part 1: Incidence of Dose-limiting toxicity (DLT) |
Time Frame: | First 21 days after the first infusion |
Safety Issue: | |
Description: | 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%. |
Secondary Outcome Measures
Measure: | Part 1 and Part 2: Objective Response Rate (ORR) |
Time Frame: | Baseline up to 30 days after last dose of study drug |
Safety Issue: | |
Description: | Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator. |
Measure: | Part 1 and Part 2: Duration of Response (DOR) |
Time Frame: | Baseline up to 30 days after last dose of study drug |
Safety Issue: | |
Description: | Duration of response will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death. |
Measure: | Part 1 and Part 2: Progression-free Survival (PFS) |
Time Frame: | Baseline up to 30 days after last dose of study drug |
Safety Issue: | |
Description: | Progression-free survival is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever comes first. |
Measure: | Part 1 and Part 2: Blood Culture Assessment of JNJ-64041757 |
Time Frame: | Periodically during treatment and up to one year after End of Treatment (EOT) visit |
Safety Issue: | |
Description: | This assessment will include the reporting of surveillance blood cultures (peripherally drawn, and through venous access device [if applicable]) for 1 year after the completion of JNJ-64041757 therapy. |
Measure: | Part 1 and Part 2: Shedding Profile of JNJ-64041757 From Cultured Samples of Feces, Urine, and Saliva |
Time Frame: | During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose) |
Safety Issue: | |
Description: | The shedding profile of JNJ-64041757 will be studied in cultures of (1) feces by stool or rectal swab, (2) urine samples, and (3) saliva samples. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Janssen Research & Development, LLC |
Trial Keywords
- Carcinoma, Non-Small-Cell Lung
- JNJ-64041757
- Listeria monocytogenes
Last Updated
November 26, 2018