A Phase Ib/IIa, Open-Label, Two-Cohort, Dose-Escalation and Dose-Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of MR001 in Patients With Locally Recurrent or Metastatic Advanced Triple-Negative Breast Cancer (TNBC) Who Have Progressed After First-Line or Later-Line Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Number of participants who experience one or more dose-limiting toxicities (DLTs)
研究概览
简要总结
This Phase Ib/IIa study is evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of MR001 in patients with advanced triple-negative breast cancer (TNBC) who have progressed after prior therapy.
详细描述
This is a dual-cohort, open-label, dose escalation and dose expansion Phase Ib/IIa study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of MR001 in patients with locally recurrent or metastatic advanced triple-negative breast cancer (TNBC) who have progressed after first-line or later-line therapy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically confirmed triple-negative breast cancer (TNBC).
- •Subjects with locally recurrent or metastatic advanced TNBC who have progressed after first-line or later-line therapy.
- •Presence of at least one measurable lesion according to RECIST V1.1 criteria.
- •ECOG Performance Status 0 or
- •Life expectancy >3 months.
- •Adequate organ and hematopoietic function based on the laboratory tests.
- •Voluntarily sign the informed consent form.
排除标准
- •History of severe allergy or hypersensitivity to the investigational product or its excipients or drugs of similar chemical class (e.g., monoclonal antibodies), or contraindications to the investigational product.
- •Requirement for systemic immunosuppressive therapy within 14 days prior to the first dose of study drug or during the study.
- •Major surgery (excluding puncture biopsy) within 4 weeks prior to the first dose of study drug, or anticipated need for major surgery during this study.
- •Uncontrolled active brain metastases or leptomeningeal metastasis.
- •History of autoimmune disease requiring treatment with corticosteroids or immunosuppressive drugs.
- •Women in the period of preconception, pregnancy, or lactation.
- •Any other circumstances which the investigator considers may increase risks to subjects or interfere with the results of the trial.
研究组 & 干预措施
Dose Escalation Part, Dose Group A: MR001 1 mg/kg, QW
干预措施: MR001 Bispecific Antibody for Injection (Drug)
Dose Escalation Part, Dose Group B: MR001 2 mg/kg, QW
干预措施: MR001 Bispecific Antibody for Injection (Drug)
Dose Escalation Part, Dose Group C: MR001 4 mg/kg, QW
干预措施: MR001 Bispecific Antibody for Injection (Drug)
Dose Escalation Part, Dose Group D: MR001 2 mg/kg, Q2W
干预措施: MR001 Bispecific Antibody for Injection (Drug)
Dose Expansion Part
Based on the Dose escalation part results, the Investigator and Sponsor will determine one dose and dosing interval to proceed to the dose expansion study
干预措施: MR001 Bispecific Antibody for Injection (Drug)
结局指标
主要结局
Number of participants who experience one or more dose-limiting toxicities (DLTs)
时间窗: Approximately 6 months
Maximum Tolerated Dose (MTD) of MR001
时间窗: Approximately 6 months
The maximum tolerated dose (MTD) of MR001 was assessed for QW dosing schedules
Incidence of Adverse Events (AEs) as Assessed by CTCAE v5.0
时间窗: Approximately 2 years
次要结局
- Recommended Phase II Dose (RP2D) based on safety, pharmacodynamics, pharmacokinetics and Preliminary Anti-tumor Activity of MR001(Approximately 6 months)
- Progression-free survival (PFS)(Approximately 2 years)
- Duration of response (DOR)(Approximately 2 years)
- Overall survival (OS)(Approximately 3 years)
- Objective Response Rate (ORR)(Approximately 2 years)
- Area Under the Plasma Concentration-Time Curve (AUC) of MR001(Predose and at designated timepoints in each cycle for approximately 2 years (each cycle = 2 weeks))
- Maximum Plasma Concentration (Cmax) of MR001(Predose and at designated timepoints in each cycle for approximately 2 years (each cycle = 2 weeks))
- Time to Maximum Plasma Concentration (Tmax) of MR001(Predose and at designated timepoints in each cycle for approximately 2 years (each cycle = 2 weeks))
- Change from baseline at different time points for TGF-β1 in plasma(Predose and at designated timepoints during the first three cycles (each cycle = 2 weeks))
- Change from baseline at different timepoints for Th1 of MR001(Predose and at designated timepoints during the first three cycles (each cycle = 2 weeks))
- Change from baseline at different timepoints for Th2 of MR001(Predose and at designated timepoints during the first three cycles (each cycle = 2 weeks))
- Incidence of Antidrug Antibodies (ADA) to MR001(Predose in each cycle for approximately 2 years (each cycle = 2 weeks))