A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10375 Monotherapy in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 354
- 试验地点
- 1
- 主要终点
- To determine the maximum tolerated dose (MTD)-Part Ia
研究概览
简要总结
HS-10375 is an oral, highly selective, small molecular inhibitor of EGFR C797S. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10375 in Chinese advanced or metastatic NSCLC.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women greater than or equal to 18 years.
- •Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .
- •Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II subjects.
- •At least one measurable lesion in accordance with RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0~
- •Estimated life expectancy >12 weeks.
- •Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
- •Females must have the evidence of non-childbearing potential.
- •Signed and dated Informed Consent Form.
排除标准
- •Treatment with any of the following:
- •Previous or current treatment with EGFR C797S inhibitors.
- •Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-
- •Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-
- •Local radiotherapy for palliation within 2 weeks of the first dose of HS-10375, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-
- •Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-
- •Inadequate bone marrow reserve or serious organ dysfunction.
- •Uncontrolled pleural, ascites or pericardial effusion.
- •Known and untreated, or active central nervous system metastases.
- •Active autoimmune diseases or active infectious disease.
- •Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications.
- •History of hypersensitivity to any active or inactive ingredient of HS-10375 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-
- •The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator.
- •The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator.
- •Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study.
- •History of neuropathy or mental disorders, including epilepsy and dementia.
研究组 & 干预措施
HS-10375
Experimental: HS-10375（Phase 1a：Dose Escalation） Subjects with advanced or metastatic NSCLC will be enrolled in dose escalation cohorts. Dose escalation of HS-10375 will be done to determine maximum tolerated dose.
Experimental: HS-10375（Phase 1b：Dose Expansion） Depending on data obtained from the dose escalation part, dose expansion may proceed with multiple cohorts in subjects with advanced or metastatic NSCLC having a EGFR C797S mutation.
Experimental: HS-10375（Phase 2） Subjects with locally advanced or metastatic EGFR C797S mutant NSCLC will be enrolled in phase 2 part to evaluate the efficacy and sufficient safety of HS-10375 as monotherapy.
干预措施: HS-10375 (Drug)
结局指标
主要结局
To determine the maximum tolerated dose (MTD)-Part Ia
时间窗: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days)
Number of participants with dose limiting toxicity
To evaluate clinical activity/efficacy of HS-10375 by assessment of objective response rate-Part Ib/II
时间窗: Time Frame: up to 24 months
Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
次要结局
- Observed maximum plasma concentration (Cmax) after single dose of HS-10375(From pre-dose to 120 hours after single dose on Day 1)
- Time to reach maximum plasma concentration (Tmax) after single dose of HS-10375(From pre-dose to 120 hours after single dose on Day 1)
- Disease Control Rate (DCR)(24 months)
- Progression-free survival (PFS)(24 months)
- Number of participants with treatment related adverse events(From baseline until 28 days after the last dose)
- Duration of response (DOR)(24 months)
- Overall survival (OS)(24 months)
- Apparent terminal half-life (T1/2) after single dose of HS-10375(From pre-dose to 120 hours after single dose on Day 1)