A Proof of Concept Study to Explore Safety and Efficacy of Tri-therapy Approach in Advanced/Metastatic NSCLC and Retrospectively Assess the Ability of Integrated Genomics and Transcriptomics to Match Patients to the Combination
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Patients with advanced/metastatic non-small cell lung cancer (NSCLC) with no documented targetable alterations (Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic Lymphoma Kinase (ALK) translocation, ROS1 mutation if available or MET exon 14 skipping mutation if available) will receive a tri-therapy associating avelumab, axitinib and palbociclib.
详细描述
During the Phase 1 (approximately 30 patients), the tri-therapy will be tested at different doses following a specific dose-escalation scheme (3 + 3 model) in order to establish the safety and identify the Maximum Tolerated Dose (MTD) and recommended dose for the Phase 2 (RP2D). The phase 2 will confirm the safety and will assess the clinical utility of the tri-therapy approach in the treatment of advanced/metastatic NSCLC (100 patients). The study will also explore the clinical utility of the Simplified Interventional Mapping System (SIMS), a new tool/algorithm enabling matching of NSCLC patients with combination therapy. For this purpose tumor/metastasis and matched normal tissue biopsies will be requested in order to obtain sequencing and expression profiles.
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
Avelumab, Axitinib, Palbociclib
For the Phase 1:
Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle).
For the Phase 2:
Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
干预措施: Avelumab (Drug)
Avelumab, Axitinib, Palbociclib
For the Phase 1:
Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle).
For the Phase 2:
Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
干预措施: Axitinib (Drug)
Avelumab, Axitinib, Palbociclib
For the Phase 1:
Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle).
For the Phase 2:
Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Baseline up to approximately 24 months
Progression Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression by RECIST 1.1 or death due to any cause, whichever occurs first.
Duration of the Response
时间窗: Baseline up to approximately 24 months
Duration of Response (DR) is defined for patients with confirmed objective response (Complete Response \[CR\] or Partial Response \[PR\]) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Overall Survival (OS)
时间窗: Baseline up to approximately 24 months
OS is defined as the time from the first dose of study treatment to the date of death due to any cause.
Incidence of the Tested 3-Drug Combination Therapy-Emergent Adverse Events and Serious Adverse Events
时间窗: From informed consent signature through 90 days after administration of the treatment (last dose)
The occurrence of adverse events and serious adverse events reported from the signing of an informed consent through 90 days after the last administration of the treatment will be summarized for all subjects who received at least one dose of the study treatment (safety population) and will be evaluated based on NCI CTCAE v4.03: June 14, 2010.
Response Rate (RR)
时间窗: Baseline up to approximately 24 months
Response rate is defined as the proportion of participants with reduction in tumor burden of a predefined amount based on RECIST 1.1 evaluation
SIMS Algorithm to Predict Clinical Outcome
时间窗: 4 years
The proportion of participants whose SIMS analysis matches the treatment combination, will be correlated retrospectively to clinical outcome.
次要结局
- Incidence of Treatment-related and or Biopsy-related Serious Adverse Events(4 years)
- Genomic and Transcriptomic Profile(4 years)