A Phase I , Single Arm, Dose Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs)
研究概览
简要总结
This is a phase I, open label, dose escalation study to evaluate tolerability, safety , pharmacokinetics and efficacy in patients with KRAS mutant NSCLC by using HL-085 and Docetaxel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •KRAS mutation NSCLC.
- •One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
- •Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment.
- •Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
- •ECOG performance status of 0-
- •Life expectancy ≥ 3 months.
- •Ability to take the medicine orally.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Hypersensitivity to study drug ingredients or their analogues.
- •Prior therapy with MEK-inhibitor.
- •Receiving any other anti-cancer therapy at the same time .
- •Active central nervous system (CNS) lesion.
- •Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
- •ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
- •Uncontrolled concomitant diseases or infectious diseases.
- •Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
- •History of HIV,HCV,HBV infection.
- •Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
- •Serum HCG test is positive.
- •Other conditions that increase the risk of study and influence the result.
研究组 & 干预措施
dose escalation of HL-085 plus Docetaxel
HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV).
f no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
干预措施: HL-085 (Drug)
dose escalation of HL-085 plus Docetaxel
HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV).
f no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Number of Adverse Events (AEs)
时间窗: Duration of the study, estimated to be approximately 24 months
Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted.
Maximum tolerated dose (MTD)
时间窗: DLTs within the first cycle of therapy (up to 35 days)
The dose level immediately below the dose level at which more than 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT)
次要结局
- Overall response rate (ORR)(Duration of the study, estimated to be approximately 24 months)
- Peak Plasma Concentration (Cmax)(Duration of the study, estimated to be approximately 24 months)
- Area under the plasma concentration verus time curve(AUC)(Duration of the study, estimated to be approximately 24 months)