A Parallel Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 161
- 试验地点
- 25
- 主要终点
- Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
研究概览
简要总结
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.
详细描述
Glesatinib is an orally administered multi-targeted tyrosine kinase inhibitor (TKI) that primarily targets the Axl and Mesenchymal-Epithelial Transition (MET) receptors. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone.
The study will begin with a lead-in dose escalation evaluation of two dose levels of each investigational agent in combination with nivolumab. Following completion of the lead-in dose escalation, enrollment into the Phase 2 study will proceed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Diagnosis of non-small cell lung cancer.
- •Prior treatment with a checkpoint inhibitor (as appropriate per cohort)
- •Adequate bone marrow and organ function
排除标准
- •Uncontrolled tumor in the brain
- •Unacceptable toxicity with prior checkpoint inhibitor
- •Impaired heart function
研究组 & 干预措施
Glesatinib and Nivolumab
Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Glesatinib (Drug)
Glesatinib and Nivolumab
Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Nivolumab (Drug)
Sitravatinib and Nivolumab
Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Sitravatinib (Drug)
Sitravatinib and Nivolumab
Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Nivolumab (Drug)
Mocetinostat and Nivolumab
Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Mocetinostat (Drug)
Mocetinostat and Nivolumab
Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
干预措施: Nivolumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
时间窗: Up to 40.6 months
ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 up to 28 days after the last dose (median time on treatment was: CIT experienced 3.7 months; CIT naïve 4.8 months))
- Duration of Response (DOR)(Up to 38.8 months)
- Progression Free Survival (PFS)(Up to 40.6 months)
- Overall Survival (OS)(Up to 43.8 months)
- Blood Plasma Concentrations(Cycle 1 Day 1 through Cycle 5 Day 1)