Pragmatica-Lung: A Prospective Randomized Study of Ramucirumab (LY3009806; NSC 749128) Plus Pembrolizumab (MK-3475; NSC 776864) Versus Standard of Care for Participants Previously Treated With Immunotherapy for Stage IV or Recurrent Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 838
- 试验地点
- 1,073
- 主要终点
- Overall survival
研究概览
简要总结
This phase III trial compares the effect of the combination of ramucirumab and pembrolizumab versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving ramucirumab with pembrolizumab is more effective at treating patients with stage IV or recurrent non-small cell lung cancer than standard chemotherapy.
详细描述
PRIMARY OBJECTIVE:
I. To compare overall survival (OS) in participants previously treated with platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC) randomized to pembrolizumab and ramucirumab versus standard of care.
SECONDARY OBJECTIVE:
I. To summarize reports of serious and unexpected high-grade (>= grade 3) treatment-related adverse events determined by the treating physician within each treatment arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
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
- •Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) which is stage IV or recurrent
- •Participants must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for any stage of NSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in combination with other therapy
- •Participants must have experienced disease progression (in the opinion of the treating physician) more than (>) 84 days following initiation (cycle 1 day 1) of their most recent anti-PD-1 or PD-L1 therapy
- •Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease, must have had a best response on anti-PD-1 or anti-PD-L1 therapy of stable, partial response or complete response (in the opinion of the treating physician)
- •Participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy as their only line of anti-PD-1 or anti-PD-L1 therapy must have experienced disease progression within (=<) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or PD-L1 therapy
- •Participants must have received platinum-based chemotherapy and experienced disease progression (in the opinion of the treating physician) during or after this regimen
- •Participants with a known sensitizing mutation for which an Food and Drug Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), must have previously received at least one of the approved therapy(s). Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria are also met
- •Participants must be >= 18 years old
- •Participants must be able to safely receive the investigational drug combination and the investigator's choice of standard of care regimens per the current FDA approved package insert(s), treating investigator's discretion, and institutional guidelines
- •Participants must have Zubrod performance status of 0-2
排除标准
- •Participants must not have received more than one line of anti-PD-1 or anti-PD-L1 for stage IV or recurrent disease
- •Participants must not be receiving or planning to receive another investigational therapy during study participation
研究组 & 干预措施
ARM B (ramucirumab, pembrolizumab)
Patients receive ramucirumab IV and pembrolizumab IV on study.
干预措施: Ramucirumab (Biological)
ARM B (ramucirumab, pembrolizumab)
Patients receive ramucirumab IV and pembrolizumab IV on study.
干预措施: Pembrolizumab (Biological)
ARM A (standard of care chemotherapy)
Patients receive chemotherapy per standard of care on study.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Overall survival
时间窗: From date of randomization to date of death due to any cause, assessed up to 3 years
Assessed in participants with stage IV or recurrent non-small cell lung cancer with acquired resistance to anti-PD-1 or anti-PD-L1 therapy randomized to ramucirumab and pembrolizumab or standard of care chemotherapy. Will use an intention-to-treat analysis and the comparison will be done using a stratified log-rank test. The distribution of overall survival will be estimated using the method of Kaplan-Meier and a Cox proportional hazards model will be used to estimate hazard ratios and associated 95% confidence intervals to estimate treatment effects.
次要结局
- Incidence of high-grade (>= grade 3) adverse events(Up to 3 years)