A Study of MR001 Combined With Chemotherapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) After First-line Therapy

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат MR001
  Intravenous infusion
• Препарат Irinotecan Liposome Injection combined with 5-FU/LV
  Per locally approved formulation
• Препарат Nab-paclitaxel
  Per locally approved formulation
• Препарат Gemcitabine (GEM)
  Per locally approved formulation

Первичные конечные точки

• Number of participants who experience one or more dose-limiting toxicities (DLTs) [Срок оценки: Approximately 12 months]
• Maximum Tolerated Dose (MTD) of MR001 [Срок оценки: Approximately 12 months]
• Incidence of Adverse Events (AEs) as Assessed by CTCAE v5.0 [Срок оценки: Approximately 30 months]
• Objective Response Rate (ORR) [Срок оценки: Approximately 24 months]
• Best Overall Response (BOR) [Срок оценки: Approximately 24 months]
• Disease control rate (DCR) [Срок оценки: Approximately 24 months]

Вторичные конечные точки (11)

• Recommended Phase II Dose (RP2D) of MR001 in combination with standard chemotherapy regimens in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) [Срок оценки: Approximately 12 months]
• Progressionfree survival (PFS) [Срок оценки: Approximately 24 months]
• Overall survival (OS) [Срок оценки: Approximately 30 months]
• Area Under the Plasma ConcentrationTime Curve (AUC) of MR001 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks)]
• Change from baseline at different time points for CD4 in plasma [Срок оценки: Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks)]

Критерии участия

Критерии включения

• 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 v1.1.
• ECOG Performance Status of 0-1.
• Life expectancy >3 months.
• Adequate organ and marrow function as defined by laboratory parameters.
• Voluntarily sign the informed consent form.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 4 центра

• Beijing Tsinghua Changgung Hospital — Пекин
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Гуанчжоу
• Harbin Medical University Cancer Hospital — Харбин
• The First Hospital of Jilin University — Changchun

Идентификаторы

NCT: NCT07235202 · MJR-MR001-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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