A Single-arm, Open-label, Multi-center Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HRS-1358 Monotherapy or Combination With Dalpiciclib Isethionate Tablets in Patients With Metastatic or Locally Advanced Breast Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
The study is being conducted to evaluate the safety and tolerability of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets in patients with metastatic or locally advanced breast cancer in order to estimate the Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D).
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
- •Histologically diagnosis of local advanced or metastatic breast cancer
- •Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression
- •At least 1 line of endocrine therapy in the metastatic or advanced setting
- •ECOG performance status score: 0-1;
- •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
- •the investigators judged that it was not suitable to endocrine therapy
- •patients with active brain metastasis (without medical control or with clinical symptoms),
- •History of clinically significant cardiovascular or cerebrovascular diseases
- •The subject has one of many factors affecting oral 、absorption, distribution, metabolism and excretion of drugs
- •Active autoimmune diseases, History of immunodeficiency, including positive HIV serum test result and other acquired or congenital immunodeficiency diseases, or history of organ transplantation
- •Have received other similar drugs in the past;
- •Known history of allergy to HRS-1358 ingredients
研究组 & 干预措施
HRS-1358
Daily oral dosages of HR-1358； Daily oral dosages of HR-1358 and Dalpiciclib Isethionate Tablets
干预措施: HRS-1358 (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: up to 28 days
The Maximum tolerated dose of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets
Dose Limited Toxicities (DLTs)
时间窗: up to 28 days
Number of participants with dose-limiting toxicities (DLTs)
RP2D
时间窗: Change From Baseline at 28 days
select the Recommended Phase 2 Dose (RP2D) of HRS-1358 or combination with Dalpiciclib Isethionate Tablets
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
次要结局
- Tmax(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Cmax(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Rac(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Duration of response (DOR) in participants(Up to approximately 1 year)
- AUC0-t(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Tmax,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Overall response rate (ORR) in participants(Up to approximately 1 year)
- Clinical benefit rate (CBR) in participants(Up to approximately 1 year)
- Progression Free Survival (PFS) observed in participants(Up to approximately 1 year)
- Cmax,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- Cmin,ss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)
- AUCss(0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period)