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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 10
- 主要终点
- Phase 1b: Percentage of Participants With Objective Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Nivolumab + JNJ-64041757
Phase 1b and Phase 2 Group A/Arm 1: Participants will receive separate intravenous (IV) infusions of nivolumab and JNJ-64041757 over approximately 60 minutes during each treatment cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
干预措施: JNJ-64041757 (Biological)
Nivolumab + JNJ-64041757
Phase 1b and Phase 2 Group A/Arm 1: Participants will receive separate intravenous (IV) infusions of nivolumab and JNJ-64041757 over approximately 60 minutes during each treatment cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
干预措施: Nivolumab (Drug)
Nivolumab
Phase 2 Group B/Arm 2: Participants will receive intravenous (IV) infusions of nivolumab over approximately 60 minutes during each treatment cycle until disease progression, unacceptable toxicity, protocol violation requiring discontinuation of study treatment, withdrawal of consent, noncompliance with study procedures, or the sponsor terminates the study.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Phase 1b: Percentage of Participants With Objective Response
时间窗: Up to 6.8 Months
Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). RECIST for CR - disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR - greater than or equal to (\>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
次要结局
- Phase 1b: Duration of Objective Response (DOR)(Up to 6.8 months)
- Phase 1b: Number of Participants With Progression-free Survival (PFS) Event (Progressed or Died Before Progression)(Up to 6.8 months)
- Phase 1b: Serum Concentrations of Nivolumab(Up to 6.8 months)
- Phase 1b: Number of Participants With Positive Blood Culture(Up to 6.8 months)
- Phase 1b: Number of Participants With Bacterial Shedding(Up to 6.8 months)
- Phase 1b: Number of Participants With Anti-nivolumab Antibodies(Up to 6.8 months)
- Phase 1b: Number of Participants With Overall Survival (OS) Event (Died)(Up to 6.8 months)
- Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to 6.8 months)