A Phase I, Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics and Clinical Activity of SYHA1807 Given Orally in Subjects With Extensive-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 71
- 主要终点
- Number of Participants Withdrawn Due to Toxicities
研究概览
简要总结
This is a phase I, open-label, multi-center, non-randomized, 2-part first time inhuman (FTIH) study for SYHA1807. Part 1 is a dose escalation phase to determine the recommended phase 2 dose (RP2D) for SYHA1807 based on the safety, tolerability and pharmacokinetics (PK) profiles observed after oral administration of SYHA1807. The dose escalation study will be performed according to the 3+3 design. Once RP2D is identified, an expansion cohort (Part 2) of up to 12~40 subjects will be enrolled to further evaluate the clinical activity and tolerability of SYHA1807 in subjects with extensive-stage Small Cell Lung Cancer (SCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of advanced SCLC;
- •ECOG(Eastern Cooperative Oncology Group) performance status of 0 or 1;
- •Measurable disease according to RECIST v1.1;
- •Recovered from all toxicities associated with previous treatments;
- •Life expectancy ≥ 3 months;
- •Adequate organ function;
- •Use of reliable contraceptive methods;
- •Signed informed consent from the patient;
排除标准
- •Patients with primary malignant tumor other than small cell lung cancer;
- •Identified central nervous system metastasis (such as brain metastasis or meningeal metastasis);
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Inadequate washout period for previous anti-tumor therapy;
- •Previous treatment with any LSD1(lysine specific demethylase 1) inhibitor;
- •Unable to swallow oral medications;
- •History of serious systemic diseases;
- •History of serious autoimmune diseases；
- •HIV positive;
- •Pregnant or lactating women.
研究组 & 干预措施
Escalation Cohort
Five dose levels will be tested according to the "3 + 3" dose-escalation design.
The dose-limiting toxicity (DLT) will be assessed from the first administration of SYHA1807 to the end of the first cycle (28 days).
干预措施: SYHA1807 (Drug)
Dose Expansion Cohort
Once the RP2D has been determined, an expansion cohort of up to 12~40 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D.
干预措施: SYHA1807 (Drug)
结局指标
主要结局
Number of Participants Withdrawn Due to Toxicities
时间窗: Through study completion, an average of 2 year
Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
Number of Participants With Dose Reduction or Delays
时间窗: Through study completion, an average of 2 year
The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.
Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline
时间窗: Through study completion, an average of 2 year
Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented.
Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug
时间窗: Through study completion, an average of 2 year
Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. The number of participants with critical changes in values of vital signs in response to drug have been presented.
Part 1:Number of Participants With Adverse Events
时间窗: Through study completion, an average of 2 year
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Part 1:Number of Participants With Serious Adverse Events (SAEs)
时间窗: Through study completion, an average of 2 year
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function.
Part 1:Number of Participants With Dose Limiting Toxicities (DLT)
时间窗: Through study completion, an average of 2 year
An event was considered a DLT if it occurs within the first 28 days of treatment.
次要结局
- Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of SYHA1807(Through study completion, an average of 2 year)
- Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of SYHA1807(Through study completion, an average of 2 year)
- Apparent Terminal Phase Elimination Rate Constant (λz) Following Single and Repeat Dose Administration of SYHA1807(Through study completion, an average of 2 year)
- Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of SYHA1807(Through study completion, an average of 2 year)
- Number of Participants Achieving Disease Control Rate at Week 6、12(Through study completion, an average of 2 year)
- Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of SYH1A1807(Through study completion, an average of 2 year)