A Phase I/II Multicenter, Open Label, Single-arm Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of WSD0922-FU in the Treatment of Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 12
- 主要终点
- ORR by IRC
研究概览
简要总结
This study is a multicenter, open label, single-arm phase I/II clinical trial of WSD0922-FU for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with thrid-generation EGFR-TKI .
详细描述
WSD0922-FU is a potent reversible inhibitor of both the single EGFRm+ and dual EGFRm+/C797S+ receptor forms of EGFR with selectivity margin over wild-type EGFR. This study aims to explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years old (including the threshold value), gender is not limited;
- •Locally advanced or metastatic NSCLC confirmed by pathology;
- •Patients who have been genetically tested to carry EGFR sensitive mutations;
- •Blood samples must be provided for testing and must be taken during or after disease progression following the last EGFR TKI inhibitor treatment;
- •Must have a minimum life expectancy of >= 3 months;
- •At least one measurable tumor lesion according to RECIST version 1.1; Previous radiotherapy-treated lesions cannot be used as target lesions unless imaging studies show clear progression of the lesions.
- •Physical Status (ECOG PS) score was 0-1;
- •Have full organ function;
- •Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method ;
- •Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily.
排除标准
- •Received chemotherapy, radiotherapy, biological therapy, targeted therapy, endocrine therapy, immunotherapy, or other anti-tumor drug treatments within 4 weeks before the first administration of the study drug.
- •Have previously received more than one EGFR-TKI inhibitor;
- •Received other unlisted clinical study drugs or treatments within 4 weeks before the first administration.
- •Received major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first administration, or require elective surgery during the trial period.
- •Used strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days before the first use of the study drug.
- •Known active brain metastasis or progression evidence.
- •Other primary malignant tumors within 2 years before the first administration of the study drug.
- •Adverse reactions from previous anti-tumor treatments have not recovered to NCI-CTCAE v5.0 grade ≤1 (except for toxicities judged by the researcher to have no safety risks, such as hair loss, grade 2 peripheral neurotoxicity, and stable thyroid function after hormone replacement therapy).
- •Skin/pressure ulcers, chronic leg ulcers, known active gastric ulcers, or non-healing wounds.
- •History of severe allergies, or allergies to any active or inactive ingredients of the study drug;
- •Severe infections requiring intravenous antibiotic infusion or hospitalization at the time of screening; or uncontrollable active infections within 4 weeks before administration;
- •Known active or suspected autoimmune diseases; or known active ocular diseases (such as active wet age-related macular degeneration, diabetic retinopathy with macular edema);
- •Human immunodeficiency virus (HIV) (HIV1/2 antibody) positive, syphilis spirochete antibody positive .
- •Patients with interstitial lung disease.
- •History of severe cardiovascular diseases.
- •Unable to orally swallow medication, or there is a condition that significantly affects gastrointestinal absorption as judged by the researcher;
- •Clinical intervention is required for pleural effusion, ascites (excluding subjects who do not need drainage and have been stable for more than 2 weeks after drainage).
- •Known alcohol or drug dependence.
- •Mental disorders or poor compliance;
- •Pregnant or lactating women;
- •The investigator believes that the subject has other reasons that make them unsuitable for participating in this clinical study.
研究组 & 干预措施
Dose escalation (WSD0922-FU)
Patients receive WSD0922-FU PO QD on C0D1 to C0D3, then BID on C1D1 to C1D21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.
干预措施: WSD0922-FU (Drug)
Dose expansion (WSD0922-FU)
Patients receive WSD0922-FU PO BID on C1D1 to C1D21 using dosage selected from Dose escalation. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.
干预措施: WSD0922-FU (Drug)
Dose extension (WSD0922-FU)
Patients receive WSD0922-FU PO BID on C1D1 to C1D21 using RP2D. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.
干预措施: WSD0922-FU (Drug)
结局指标
主要结局
ORR by IRC
时间窗: every 6 weeks, up to 1 year
proportion of patients with a best overall response of complete response or partial response
PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC
时间窗: 8 months
Safety (incidence and severity of adverse events \[AE\])
PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC
时间窗: 8 months
Incidence and quantity of dose-limiting toxicity (DLT)
PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC
时间窗: 8 months
Incidence of Dose-Limiting Toxicities (DLTs)
PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC
时间窗: 8 months
Recommended Phase II Dose (RP2D)
次要结局
- PK exposure parameter: Maximum Plasma Concentration (Cmax)(12 months)
- PK exposure parameter: Time To Maximum Plasma Concentration (Tmax)(12 months)
- PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t)(12 months)
- PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)(12 months)
- PK exposure parameter: Terminal Elimination Half-Life (t½)(12 months)
- PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz)(12 months)
- PK exposure parameter: Apparent Clearance (CL)(12 months)
- PK exposure parameter: Apparent volume of distribution (Vd)(12 months)
- PK exposure parameter: Mean Residence Time (MRT)(12 months)
- Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss）(12 months)
- Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss）(12 months)
- Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss）(12 months)
- Steady state pharmacokinetic parameter: Average Steady-State Concentration（Cav）(12 months)
- Steady state pharmacokinetic parameter: Steady-State Clearance（CLss）(12 months)
- PK exposure parameter :Maximum Steady-State Concentration（Cmax,ss）(12 months)
- PK exposure parameter : Minimum Steady-State Concentration（Cmin,ss）(12 months)
- PK exposure parameter : Trough Concentration（Ctrough）(12 months)
- PK exposure parameter : Fluctuation Degree（DF）(12 months)
- PK exposure parameter : Accumulation Ratio（Ra）(12 months)
- PK exposure parameter : Time to Maximum Concentration at Steady State（Tmax,ss）(12 months)
- PK exposure parameter : Volume of Distribution Calculated from the Terminal Elimination Phase（Vz）(12 months)
- To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer(12 months)
- ORR by investigators(every 6 week, up to 12 months)
- Disease Control Rate (DCR)(every 6 weeks, up to12 months)
- Duration of Response (DoR)(every 6 weeks, up to 12 months)
- PFS(every 6 weeks, up to 12 months)
- OS(24 months)