Intrathecal Administration of Dual Checkpoint Inhibitor in Combination With Pemetrexed in Patients With Leptomeningeal Metastasis: a Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 34
- 试验地点
- 5
- 主要终点
- PR2D
研究概览
简要总结
This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with QL1706) in combination with pemetrexed in patients with leptomeningeal metastasis.
详细描述
This study is a prospective, single-arm, phase I/II clinical trial evaluating intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with the bispecific antibody QL1706) in combination with pemetrexed for the treatment of leptomeningeal metastasis.
Intrathecal pemetrexed is administered twice weekly for 2 weeks (induction phase), then weekly for 4 weeks (consolidation phase), and monthly thereafter (maintenance phase). Intrathecal QL1706 (a co-formulation of separate anti-PD-1 and anti-CTLA-4 antibodies) is given every two weeks during the six-week （induction and consolidation phase）, followed by monthly injections in the maintenance phase, until disease progression or death.
The primary objectives are to determine the recommended dose of intrathecal QL1706 in combination with pemetrexed and to assess safety based on the incidence of treatment-related adverse events. Clinical response rate, disease control rate, and overall survival are also evaluated. Patients undergo cerebrospinal fluid and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.
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
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
- •Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm
- •No history of severe nervous system disease; No severe dyscrasia.
排除标准
- •Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than
- •Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
- •A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing >Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.
- •Patients with poor compliance or other reasons that were unsuitable for this study.
研究组 & 干预措施
Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed
This study is a prospective, single-arm, Phase I/II clinical trial. The primary objectives were to determine the recommended dose of intrathecal dual checkpoint inhibitor (PD-1 and CTLA-4, QL1706) in combination with pemetrexed and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen.
干预措施: QL1706 (bispecific antibody targeting PD-1 and CLTA-4) (Drug)
Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed
This study is a prospective, single-arm, Phase I/II clinical trial. The primary objectives were to determine the recommended dose of intrathecal dual checkpoint inhibitor (PD-1 and CTLA-4, QL1706) in combination with pemetrexed and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen.
干预措施: Pemetrexed (Alimta) (Drug)
结局指标
主要结局
PR2D
时间窗: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.
Incidence of treatment-related adverse events
时间窗: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events.
RP2D
时间窗: Dose limiting toxicity was assessed during the first 6 weeks after the first intrathecal administration.
The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g.,meningitis) or other grade 4 toxicity.
次要结局
未报告次要终点
研究者
Zhenyu Pan
Professor
Guangzhou Medical University