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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (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) [Time frame: Approximately 12 months]
• Progressionfree survival (PFS) [Time frame: Approximately 24 months]
• Overall survival (OS) [Time frame: Approximately 30 months]
• Area Under the Plasma ConcentrationTime Curve (AUC) of MR001 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Predose and at designated timepoints in each cycle for approximately 18 months (each cycle = 2 weeks or 4 weeks)]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

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

Identifiers

NCT: NCT07235202 · MJR-MR001-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗