A Phase I/II Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of WSD0922-FU in Combination With Osimertinib for Patients With Locally Advanced or Metastatic 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
- 48
- 试验地点
- 1
- 主要终点
- PartA: To evaluate the safety of WSD0922-FU combined with Osimertinib in patients with NSCLC
研究概览
简要总结
This is a Phase I/II, Open Label Study of WSD0922-FU in Combination with Osimertinib for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose disease has progressed with third-generation EGFR-TKI with C797S mutation or is newly diagnosed with CNS metastasis with EGFR Del19 or L858R mutation
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 combined with Osimertinib in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance, and then further confirm the safety and efficacy for newly diagnosed NSCLC BM patients with classical EGFR Del19 or L858R mutation
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥Age 18, gender is not limited;
- •Locally advanced or metastatic NSCLC confirmed by pathology;
- •Patients who have been genetically tested to carry EGFR sensitive mutations;
- •Blood/Tissue samples must be provided for testing;
- •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 two EGFR-TKI inhibitors for part A;
- •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 drugs.
- •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 and Osimertinib)
Patients receive 80mg Osimertinib PO QD and WSD0922-FU PO QD. 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: Osimertinib (Tagrisso®) (Drug)
Dose escalation (WSD0922-FU and Osimertinib)
Patients receive 80mg Osimertinib PO QD and WSD0922-FU PO QD. 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 and Osimertinib)
Patients receive 80mg Osimertinib PO QD and WSD0922-FU PO QD 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: Osimertinib (Tagrisso®) (Drug)
Dose expansion (WSD0922-FU and Osimertinib)
Patients receive 80mg Osimertinib PO QD and WSD0922-FU PO QD 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)
结局指标
主要结局
PartA: To evaluate the safety of WSD0922-FU combined with Osimertinib in patients with NSCLC
时间窗: 12 months
Safety (incidence and severity of adverse events \[AE\])
PartB: To evaluate the efficacy of WSD0922-FU combined with Osimertinib in patients with NSCLC
时间窗: every 6 weeks, up to 2 years
ORR
次要结局
- Disease Control Rate (DCR)(every 6 weeks, up to 24 months)
- To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer(12 months)
- Duration of Response (DoR)(every 6 weeks, up to 24 months)
- PFS(every 6 weeks, up to 24 months)
- Intracranial Disease Control Rate (iDCR)(every 6 weeks, up to24 months)
- Intracranial Duration of Response (iDoR)(every 6 weeks, up to 24 months)
- iPFS(every 6 weeks, up to 24 months)