Clinical trial NCT03371381: An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung
Official title: An Open-Label Randomized Phase 1b/2 Study of the Efficacy and Safety of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Subjects With Advanced Adenocarcinoma of the Lung
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma of Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-12-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether the efficacy of JNJ-757 combined with nivolumab is better than the efficacy of nivolumab monotherapy for participants with mesothelin-positive relapsed/refractory Stage IIIB or Stage IV adenocarcinoma of the lung. The open-label study comprises of two parts i.e. Phase 1b (safety run-in) and Phase 2. Phase1b consists of 1 arm whereas Phase 2 is randomized into 2 groups i.e. Group A and Group B.

Detailed description: This study evaluates safety and efficacy of JNJ-64041757 with nivolumab. The total study duration will be up to 3 years. It will consist of safety run-in and randomized phase which will comprise of Screening phase(Day(D) -28 to D -1),Treatment Phase,End of Adverse Event Evaluation Period (100 D after last dose of nivolumab)and Post-treatment Follow-up Phase(Every 3 Months). The primary hypothesis is that addition of JNJ-640417577 to nivolumab will result in higher objective response rate compared with nivolumab monotherapy in at least one of programmed death receptor ligand 1 subgroups in participants with relapsed or refractory StageIIIB or StageIV adenocarcinoma of lung. The study procedures include blood culture bacterial shedding assessments, pharmacokinetics, immunogenicity, and biomarkers. Safety will be monitored throughout study.

Eligibility criteria: Inclusion Criteria:

* Disease-related criteria: Histologically documented adenocarcinoma of the lung; Stage IIIB or Stage IV disease; Biopsy material available for central assessment of programmed death receptor ligand 1 (PD-L1) and mesothelin
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Progressive disease during or after platinum-based doublet chemotherapy
* A woman of childbearing potential must have a negative serum or urine pregnancy test within 14 days before the first dose of nivolumab
* Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

* Tumor with activating epidermal growth factor receptor (EGFR) mutation or ALK translocation
* More than 1 prior line of chemotherapy for metastatic disease (Phase 2)
* History of disallowed therapies, as follows: In Phase 1b only: Prior exposure to anti-programmed death receptor-1(PD1), anti programmed death receptor ligand 1 (PD-L1), anti-programmed death receptor ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody within 28 days before the first dose of study agent, In Phase 2 only: Prior exposure to anti-PD1, anti PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody, History of listeriosis or vaccination with a Listeria-based vaccine or prophylactic vaccine within 28 days before the first dose of study agent, Chemotherapy within 28 days before the first dose of study agent, Radiation within 14 days before the first dose of study agent
* History of any other condition that may require the initiation of anti-tumor necrosis factor alpha (TNF alpha) therapies or other immunosuppressant medications during the study
* Active second malignancy within 2 years prior to Cycle 1 Day 1 (Phase 1b) or randomization (Phase 2)

Primary outcomes:
measure: Phase 1b: Percentage of Participants With Objective Response
timeFrame: Up to 6.8 Months
Secondary outcomes:
measure: Phase 1b: Duration of Objective Response (DOR)
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Positive Blood Culture
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Bacterial Shedding
timeFrame: Up to 6.8 months
measure: Phase 1b: Serum Concentrations of Nivolumab
timeFrame: Up to 6.8 months
measure: Phase 1b: Number of Participants With Anti-nivolumab Antibodies
timeFrame: Up to 6.8 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Barcelona
country: Spain
facility: Hosp. Univ. Quiron Dexeus
city: Elche
country: Spain
facility: Hosp. Gral. Univ. de Elche
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaen
city: Málaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Palma de Mallorca
country: Spain
facility: Hosp. Son Llatzer
city: Valencia
country: Spain
facility: Hosp. Arnau de Vilanova de Valencia
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: