An Open-label, Dose-escalation and Dose-expansion Phase Ib/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of MR001 in Combination With Standard Chemotherapy Regimens in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Who Have Progressed After First-line Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 4
- 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 Combined with Chemotherapy in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have progressed after first-line therapy.
详细描述
This is an open-label, dose-escalation and dose-expansion Phase Ib/IIa study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of MR001 in combination with standard chemotherapy regimens in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have progressed after first-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
- •Histologically or cytologically confirmed locally advanced or metastatic PDAC, progressed after only one prior line of systemic therapy.
- •At least one measurable lesion per RECIST v1.
- •ECOG Performance Status of 0-
- •Life expectancy >3 months.
- •Adequate organ and marrow function as defined by laboratory parameters.
- •Voluntarily sign the informed consent form.
排除标准
- •Known hypersensitivity to MR001 or similar monoclonal antibodies.
- •Requirement for systemic immunosuppressive therapy within 14 days before first dosing.
- •Uncontrolled active infections or concurrent malignancies.
- •Not adequately controlled active brain metastases or leptomeningeal metastasis.
- •Clinically significant cardiovascular, renal, or hepatic disorders.
- •Pregnant or breastfeeding women.
- •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 Part1, Dose Group 1: MR001+Irinotecan Liposome+LV/5-FU
MR001, 2mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: Irinotecan Liposome Injection combined with 5-FU/LV (Drug)
Dose Escalation Part1, Dose Group 2: MR001+Irinotecan Liposome+LV/5-FU
MR001, 4mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: Irinotecan Liposome Injection combined with 5-FU/LV (Drug)
Dose Escalation Part1, Dose Group 3: MR001+Irinotecan Liposome+LV/5-FU
MR001, 6mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part2, Dose Group 2: MR001+nab-paclitaxel+gemcitabine
MR001, 4mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part1, Dose Group 1: MR001+Irinotecan Liposome+LV/5-FU
MR001, 2mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part1, Dose Group 2: MR001+Irinotecan Liposome+LV/5-FU
MR001, 4mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part2, Dose Group 2: MR001+nab-paclitaxel+gemcitabine
MR001, 4mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Gemcitabine (GEM) (Drug)
Dose Escalation Part2, Dose Group 2: MR001+nab-paclitaxel+gemcitabine
MR001, 4mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Nab-paclitaxel (Drug)
Dose Escalation Part1, Dose Group 3: MR001+Irinotecan Liposome+LV/5-FU
MR001, 6mg/kg, QW; Irinotecan Liposome+LV/5-FU, Per locally approved dosage and administration
干预措施: Irinotecan Liposome Injection combined with 5-FU/LV (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: Irinotecan Liposome Injection combined with 5-FU/LV (Drug)
Dose Escalation Part2, Dose Group 1: MR001+nab-paclitaxel+gemcitabine
MR001, 2mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part2, Dose Group 1: MR001+nab-paclitaxel+gemcitabine
MR001, 2mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Nab-paclitaxel (Drug)
Dose Escalation Part2, Dose Group 1: MR001+nab-paclitaxel+gemcitabine
MR001, 2mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Gemcitabine (GEM) (Drug)
Dose Escalation Part2, Dose Group 3: MR001+nab-paclitaxel+gemcitabine
MR001, 6mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: MR001 (Drug)
Dose Escalation Part2, Dose Group 3: MR001+nab-paclitaxel+gemcitabine
MR001, 6mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Nab-paclitaxel (Drug)
Dose Escalation Part2, Dose Group 3: MR001+nab-paclitaxel+gemcitabine
MR001, 6mg/kg, QW; nab-paclitaxel+gemcitabine, Per locally approved dosage and administration
干预措施: Gemcitabine (GEM) (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 (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: Nab-paclitaxel (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: Gemcitabine (GEM) (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 12 months
Maximum Tolerated Dose (MTD) of MR001
时间窗: Approximately 12 months
The maximum tolerated dose (MTD) of MR001 was assessed for QW dosing schedules
Objective Response Rate (ORR)
时间窗: Approximately 24 months
Disease control rate (DCR)
时间窗: Approximately 24 months
Incidence of Adverse Events (AEs) as Assessed by CTCAE v5.0
时间窗: Approximately 30 months
Best Overall Response (BOR)
时间窗: Approximately 24 months
次要结局
- Recommended Phase II Dose (RP2D) of MR001 in combination with standard chemotherapy regimens in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)(Approximately 12 months)
- Progressionfree survival (PFS)(Approximately 24 months)
- Change from baseline at different time points for CD4 in plasma(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Overall survival (OS)(Approximately 30 months)
- Area Under the Plasma ConcentrationTime Curve (AUC) of MR001(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Half-life (T1/2) of MR001(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Change from baseline at different timepoints for Th2 in plasma(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Maximum Plasma Concentration (Cmax) of MR001(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Incidence of Antidrug Antibodies (ADA) to MR001(Predose in every 4 cycles for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Change from baseline at different time points for Th1 in plasma(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))
- Change from baseline at different timepoints for TGF-β1 in plasma(Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks))