A Single-arm, Open-label and Multi-center Phase I Study on Safety, Tolerance and Pharmacokinetics of HRS-8080 Tablets Monotherapy and Combined With Other Anti-cancer Therapy in Patients With Metastatic or Local Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 156
- 试验地点
- 2
- 主要终点
- Incidence and severity of adverse events (AEs)/serious adverse events (SAEs)
研究概览
简要总结
The study is being conducted to evaluate the tolerance, and safety of HRS-8080 tablets monotherapy and combined with other anti-cancer therapy for metastatic or local advanced breast cancer in adults. To explore the reasonable dosage of HRS-8080 tablets for metastatic or local advanced breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status score: 0-1;
- •Histopathologically documented local advanced or metastatic breast cancer ;
- •Female of not childbearing potential must the related requirement;
- •During or after the last systematic therapy before enrolment, disease progression occurred with clinical or radiographical documentation;
- •Adequate organ functions as defined;
- •Ability to understand and voluntarily agrees to participate by giving written informed consent for the study.
排除标准
- •For the case of symptomatic visceral metastasis, the investigators judged that it was not suitable to use relevant treatment;
- •patients with active brain metastasis (without medical control or with clinical symptoms), cancerous meningitis, spinal cord compression, or patients with a history of primary tumors of the central nervous system ;
- •History of clinically significant cardiovascular or cerebrovascular diseases;
- •The subject has one of many factors affecting oral drugs;
- •Active infection or fever with unknown cause > 38.5 °C;
- •Active autoimmune diseases, History of immunodeficiency, including positive HIV serum test result and other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
- •Known history of allergy to study drug ingredients.
研究组 & 干预措施
Single Group
Firstly Dose Escalation and Dose Expansion of HRS-8080 monotherapy should be conducted. After RP2D and MTD of the HRS-8080 monotherapy were confirmed, Dose Escalation and Dose Extension of HRS-8080 in combination with other anti-cancer treatment would be completed, including SHR 6390, or Abemaciclib, or Everolimus.
干预措施: HRS-8080 tablets、SHR 6390 tablets、Abemaciclib、Everolimus (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs)
时间窗: up to 30 days after the last dose
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Recommended phase II dose
时间窗: up to 28 days
The Recommended phase II dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus
Maximum tolerated dose
时间窗: up to 28 days
The Maximum tolerated dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus
次要结局
- AUCss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Cmin,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Cmax(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Tmax(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- AUC0-t(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Cmax,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Tmax,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- Rac(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period)
- ORR(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months)
- BOR(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months)
- DoR(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months)
- DCR(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months)
- PFS(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months)