NCT06050980招募中1 期
A Phase I, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of HSK40118 in Patients With EGFR Mutation Locally Advanced or Metastatic NSCLC
Haisco Pharmaceutical Group Co., Ltd.12 个研究点 分布在 1 个国家目标入组 220 人开始时间: 2023年3月27日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 12
- 主要终点
- MTD
研究概览
简要总结
This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and PD of HSK40118 when given orally in patients with active EGFR mutation locally advanced or metastatic non-small cell lung cancer (NSCLC).
The study will contain two phase: Phase Ia is dose escalation phase and Phase Ib is dose expansion phase.
详细描述
Phase Ia will contain two part: Dose Escalation Part(Part A) and Extension Part(Part B). Part A based on the "3+3" design for dose escalation and safety evaluation requirements. Patient cohorts at selected doses may be extended to further investigate the tolerability, PK and PD of HSK40118. The number of patients to be enrolled will be up to 10 subjects in each Part B cohort. Approximately 30-70 subjects will be enrolled in Phase Ia.
Phase Ib no less than 130 subjects will be enrolled in each expansion cohort, cohort A will be enrolled 30-50 subjects, cohort B will be enrolled no less than 100 subjects.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years, Male and female patients, at time of signing informed consent form (ICF).
- •ECOG=0-1, with no deterioration in 2 weeks before first dose of HSK
- •Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
- •Patients will provide blood or tumor sample according to their own willingness.
- •Patients in Phase Ia and Ib will fulfill the different criteria of the following:
- •Phase Ia(Part A): Previous treatment with at least one EGFR-TKI, including 1st, 2nd and 3rd-generation EGFR-TKI; Phase Ia(Part B)/Phase Ib: Previous treatment with 3rd-generation EGFR-TKI.
- •tumour lesions/lymph nodes: Phase Ia(Part A): Patients should have at least one assessable tumour lesions/malignant lymph nodes; Phase Ia(Part B) /Phase Ib: Patients should have at least one measurable tumour lesions/malignant lymph nodes.
- •Life expectancy ≥ 3 months.
- •Adequate hematologic and organ function per protocol.
- •Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception per protocol throughout and after 90 days of the last dose of the study.
排除标准
- •malignant tumor within 5 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
- •Unstable spinal cord compression or brain metastases per protocol.
- •Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
- •Prior treatment with 4th-generation EGFR-TKIs(TKI for 3th-generation resistance).
- •Treatment with any of the following:
- •Prior treatment with an EGFR-TKI or other small-molecule anti-tumor drug within 7 days or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with chemotherapy, palliative radiotherapy, or Herbal therapy within 2 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with radiotherapy, immunotherapy/biotherapy therapy, or other pharmaceutical clinical trial within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter.
- •Treatment with inhibitors for P-glycoprotein (P-gp) within 7 days prior to the first dose of HSK
- •Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
- •Any disease which would cause chronic diarrhea, eg. Crohn's disease, or irritable bowel syndrome.
- •Any disease which would preclude drug absorption, metabolism or pharmacokinetics, eg. active peptic ulcer or chronic gastroesophageal reflux disease.
- •Any severe disease of respiratory system, eg. interstitial lung disease, radiation pneumonitis, drug-induced pneumonitis, or uncontrolled asthma.
- •Patient who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450(male)/470(female) msec; any clinically significant arrhythmia; left ventricular ejection fraction < 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK
- •Any thromboembolic events within 6 months prior to the first dose of HSK40118; any familial or aquired thrombophilia.
- •Active bleeding at screening, history of visceral hemorrhage within 3 months prior to the first dose of HSK40118, or visceral bleeding tendency within 6 months prior to the first dose of HSK
- •Patient who is undergoing, or receiving long-term(> 6 months) anticoagulant/antiplatelet therapy; receiving drugs affecting coagulation function 1 week prior to the first dose of HSK
- •INR, APTT > 1.5xULN, or any bleeding tendency or coagulopathy at screening.
- •Uncontroled hypertension(systolic pressure ≥160mmHg, or diastolic pressure ≥100mmHg).
- •Any unstable systemic disease, eg. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
- •Any disease of the eyes > CTCAE v5.0 Grade
- •Autologous transplantation surgery within 3 months prior to the first dose of HSK40118; Allogeneic transplantation, or stem-cell Transplant surgery within 6 months prior to the first dose of HSK40118; Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of HSK
- •Patients with HIV, HBV or HCV infection.
- •Patients with active syphilis infection.
- •Patients who have an uncontroled systematic infection, eg. fungal, bacterial, or virus infection.
- •Patients who would interfere with cooperation or outcome-assessment of the trial.
- •Allergic to any HSK40118 active constituent or ingredients.
- •(Child-bearing period women only)Patients testing positive for pregnancy, or during lactation.
- •Any other circumstances that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
研究组 & 干预措施
Phase Ia(Part A): HSK40118 as monotherapy
Experimental
Phase 1a(Part A): dose escalation of HSK40118 as monotherapy at various dose levels
干预措施: HSK40118 (Drug)
Phase Ia(Part B): HSK40118 as monotherapy
Experimental
Phase 1a(Part B): dose extention of HSK40118 as monotherapy at certain dose levels
干预措施: HSK40118 (Drug)
Phase Ib: HSK40118 as monotherapy
Experimental
Phase 1b: dose expansion for HSK40118 as monotherapy at a dose determined during Phase 1 in patients with previous treatment with 3rd-generation EGFR-TKI
干预措施: HSK40118 (Drug)
结局指标
主要结局
MTD
时间窗: Up to approximately 52 months
MTD determination: dose limiting toxicity (DLT) rate
Eastern Cooperative Oncology Group Performance Status Scale(ECOG PS)
时间窗: Up to approximately 52 months
Change of the grade as a part of HSK40118 safety data. The functional status of patients will be assessed by the ECOG PS, which is described as a scale including grade 0(fully active) to grade 5(dead).
DLTs
时间窗: Up to approximately 52 months
Incidence of dose-limiting toxicities (DLTs) at Cycle 0 and Cycle1
AEs
时间窗: Up to approximately 52 months
Rate and severity of adverse events of HSK40118 as monotherapy
次要结局
- Overall response rate(ORR)(Up to approximately 52 months)
- Disease control rate (DCR)(Up to approximately 52 months)
- Overall survival (OS)(Up to approximately 52 months)
- AUC of HSK40118(Blood samples will be collected on 6 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3, cycle 1 day 1, cycle 1 day 8 and cycle 1 day 15.)
- Cmin of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 1 day 1, cycle 1 day 8 and cycle 1 day 15.)
- Tmax of HSK40118(Blood samples will be collected on 6 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3, cycle 1 day 1, cycle 1 day 8 and cycle 1 day 15.)
- Terminal half life(t1/2) after single dosing of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3.)
- Vd/F of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3.)
- λz of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3.)
- Cav,ss(average concentration at steady state) of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 1 day 1, cycle 1 day 8 and cycle 1 day 15.)
- Duration of response (DOR)(Up to approximately 52 months)
- Progression free survival (PFS)(Up to approximately 52 months)
- Cmax of HSK40118(Blood samples will be collected on 6 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3, cycle 1 day 1, cycle 1 day 8 and cycle 1 day 15.)
- CL/F of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3.)
- MRT(Mean residence time) of HSK40118(Blood samples will be collected on 3 occasions for each patient throughout study: cycle 0 day 1, cycle 0 day 2, cycle 0 day 3.)
研究者
研究点 (12)
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