A Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of AXL Inhibitor FC084CSA Tablets in Combination With Tislelizumab in the Treatment of Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
The goal of this clinical trial is to learn the safety, tolerability, pharmacokinetic characteristics and efficacy of FC084CSA in combination with Tislelizumab in patients with advanced malignant solid tumors.
详细描述
The study includes two phases. Phase Ib adopts a "3+3" dose escalation design to assess safety and tolerability of increasing dose levels of FC084CSA in combination of fixed dose of Tislelizumab. Phase IIa is the dose expansion phase to further observe the preliminary effectiveness of the recommended Phase 2 Dose of FC084CSA in combination of Tislelizumab.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years old male and female.
- •Phase Ib: Patients with histologically or cytologically diagnosed solid tumors who have failed standard therapy; Phase IIa: Patients with histologically or cytologically confirmed stage IIIB/IIIC and stage IV NSCLC which surgery or radiotherapy cannot be performed.
- •No known sensitizing mutations or other actionable oncogenes with approved therapies if available.
- •Prior PD-1/PD-L1 inhibitor combined with platinum-containing therapy failed;
- •According to RECIST 1.1, there is at least one measurable lesion.
- •ECOG performance status 0-
- •Major organs are functioning well.
排除标准
- •Not recovered from the adverse reactions caused by previous anti-tumor treatments (≥CTCAE grade 1).
- •Received anti-tumor therapy within 4 weeks before enrollment.
- •Participated in other clinical trials within 4 weeks before enrollment and used clinical investigational drugs during this period.
- •Have undergone surgery within 4 weeks before enrollment, and the investigator believes that the patient's state has not recovered to the point where the study can be started.
- •Patients with ascites (ascites), pleural effusion (pleural effusion) or pericardial effusion that cannot be controlled by drainage or other methods.
- •Central nervous system metastases with clinical symptoms.
- •With any situations that the researcher considers inappropriate to participate in this research.
研究组 & 干预措施
FC084CSA+Tislelizumab
This is a single arm phase I trial in a 3 + 3 dose escalation and cohort expansion design evaluating the safety and tolerability of FC084CSA in combination with Tislelizumab. Increasing dose levels of FC084CSA with fixed dose of Tislelizumab. Dose escalation continues until dose-limiting toxicities (DLT) are observed in one-third of participants. If no DLT occurs, the next cohort will be enrolled at the next planned dose level. If 1 DLT occurs in a cohort, another 3 patients will be treated with the same dose level. Following the definition of the recommended Phase 2 Dose (RP2D) of FC084CSA in dose escalation phase, NSCLC dose expansion cohort is planned to perform a preliminary assessment of the anti-tumour efficacy and to further establish the safety profile of the RP2D of FC084CSA in combination with Tislelizumab.
干预措施: FC084CSA+Tislelizumab combination (dose escalation) (Drug)
FC084CSA+Tislelizumab
This is a single arm phase I trial in a 3 + 3 dose escalation and cohort expansion design evaluating the safety and tolerability of FC084CSA in combination with Tislelizumab. Increasing dose levels of FC084CSA with fixed dose of Tislelizumab. Dose escalation continues until dose-limiting toxicities (DLT) are observed in one-third of participants. If no DLT occurs, the next cohort will be enrolled at the next planned dose level. If 1 DLT occurs in a cohort, another 3 patients will be treated with the same dose level. Following the definition of the recommended Phase 2 Dose (RP2D) of FC084CSA in dose escalation phase, NSCLC dose expansion cohort is planned to perform a preliminary assessment of the anti-tumour efficacy and to further establish the safety profile of the RP2D of FC084CSA in combination with Tislelizumab.
干预措施: RP2D of FC084CSA+Tislelizumab combination (dose expansion) (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Approximately 12 months
To explore the clinical effectiveness. Tumor response based on RECIST 1.1
Determine the Maximum Tolerated Dose (MTD)
时间窗: Approximately 8 months
The highest dose is defined at which no more than 1 of 3 evaluable participants has had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria and determination by Investigator and Data and Safety Monitoring Committee.
Determine dose-limiting toxicity (DLT)
时间窗: 21 days after first dose
Determine the DLT of FC084CSA
Determine the Recommended Phase 2 Dose (RP2D)
时间窗: Approximately 8 months
The RP2D is based upon the review of all available data including safety, pharmacokinetic, preliminary anti-tumor activity, and MTD.
次要结局
- Disease control rate (DCR)(Approximately 12 months)
- Progression free survival (PFS)(Approximately 12 months)
- Pharmacokinetic (PK) AUC 0-t(Approximately 12 months)
- Pharmacokinetic (PK) Cmax(Approximately 12 months)
- Pharmacokinetic (PK) AUC 0-∞(Approximately 12 months)
- Overal suvival (OS)(Approximately 18 months)
- Pharmacokinetic (PK) Tmax(Approximately 12 months)