A Phase II Study of LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Proportion of Participants With Partial Response or Complete Response Reported With an 95% Confidence Interval
研究概览
简要总结
Background:
Over 230,000 new lung cancer cases are diagnosed every year in the United States (U.S.) About 80% of lung cancers are non- small cell lung cancer (NSCLC). Most people have a more advanced stage of the disease that doesn't respond well to standard treatment. Researchers want to see if a combination of drugs may be able to help.
Objective:
To find out if LMB-100 followed by pembrolizumab can help tumors to shrink in people with NSCLC.
Eligibility:
People ages 18 and older with NSCLC that has not responded to standard therapies
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Tumor sample. If one is not available, they will have a biopsy.
- Assessments of ability to perform normal activities
- Lung function tests
- Blood, heart, and urine tests
- Computed tomography (CT) and positron emission tomography (PET). They will lie in a machine that takes pictures of the body.
Participants will take LMB-100 in 21-day cycles for up to 2 cycles. They will take the drug by injection into an arm vein on days 1, 3, and 5 of each cycle. They will stay in the hospital 7-10 days each cycle. Then they will get pembrolizumab by injection into an arm vein every 3 weeks for up to 2 years. They may be able to take pembrolizumab an additional year if their cancer gets worse.
Participants will have repeats of the screening tests throughout the study.
About 30 days and 90 days after they stop treatment, participants will have follow-up visits. Then they will have visits every 6-12 weeks. They will be followed for the rest of their life through phone calls and emails.
详细描述
Background:
- Mesothelin is expressed in approximately half of all lung adenocarcinomas.
- LMB-100 has demonstrated anti-tumor efficacy against several mesothelin expressing tumor models including non-small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-1) is an Ig superfamily member related to cluster of differentiation (CD28) and cluster of differentiation 152 (CTLA-4) that has been shown to negatively regulate antigen receptor signaling upon engagement of its ligands.
- Pembrolizumab, an immunoglobulin G4 (IgG4) monoclonal antagonist antibody to PD-1, is Food and Drug Administration (FDA) approved in the frontline for advanced non-squamous NSCLC as a single agent with high programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) >=50%] or in combination with platinum-based doublet chemotherapy (PD-L1 unselected). It also approved in the second-line for high PDL1 expressing tumors (TPS >=1%).
- Combination treatment with LMB-100 plus pembrolizumab results in greater anti-tumor efficacy in murine lung cancer model.
Objectives:
-To determine the objective response rate of LMB-100 followed by pembrolizumab in the treatment of subjects with mesothelin-expressing non-squamous non-small cell lung cancer (NSCLC) previously treated with immune checkpoint inhibitors.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Mesothelin Expressing Non-Small Cell Lung Cancer Participants
LMB-100 + Pembrolizumab
干预措施: LMB-100 (Drug)
Mesothelin Expressing Non-Small Cell Lung Cancer Participants
LMB-100 + Pembrolizumab
干预措施: pembrolizumab (Drug)
Mesothelin Expressing Non-Small Cell Lung Cancer Participants
LMB-100 + Pembrolizumab
干预措施: Mesothelin Expression (Diagnostic Test)
Mesothelin Expressing Non-Small Cell Lung Cancer Participants
LMB-100 + Pembrolizumab
干预措施: TrueSight Oncology 500 (Diagnostic Test)
结局指标
主要结局
Proportion of Participants With Partial Response or Complete Response Reported With an 95% Confidence Interval
时间窗: End of treatment, an average of 83 days.
Participants with a partial response or complete response is reported with an 95% confidence interval. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Proportion of Participants With Partial Response or Complete Response Reported With an 80% Confidence Interval
时间窗: End of treatment, an average of 83 days.
Participants with a partial response or complete response is reported with an 80% confidence interval. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- Overall Survival(Time from the start of treatment to death from any cause, a median of 22.9 months)
- Progression Free Survival (PFS)(Time from start of treatment to time of progression (on or after pembrolizumab) or death, whichever occurs first, calculated from the on-study date using the Kaplan-Meier method, an average of 2.7 months.)
- Proportion of Participants With Grade 3 and Grade 4 Adverse Events Possibly, Probably, and Definitely Related to Pembrolizumab(Date treatment consent signed to date off study, approximately 48.7 months)
- Number of Participants With a Response(Beginning at the date a participant is noted to have at least a partial response (PR), an average of 2.7 months.)
- Number of Participants Who Are Treated Who Are Unable to Tolerate the Treatment Other Than Development of Adverse Events(Date treatment consent signed to date off study, approximately 48.7 months)
- Overall Response (OR)(From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease), an median of 22.9 months.)
- Proportion of Participants With Grade 3 and Grade 4 Adverse Events Possibly, Probably, and Definitely Related to LMB-100(Date treatment consent signed to date off study, approximately 48.7 months)
研究者
Azam Ghafoor
Principal Investigator
National Cancer Institute (NCI)