Chimeric Antigen Receptor Macrophages Targeting c-MET for Advanced Stage of Pancreatic Cancer Patients

Prior treatment

• Received the following anti-tumor treatments prior to apheresis: Immunomodulatory therapy within 7 days; Cytotoxic therapy within 14 days; Investigational medication, targeted therapy, or anti-tumor traditional Chinese medicine within 28 days.
• Previously received CAR-T cell therapy or other cell therapies targeting any antigen.
• History of other concurrent malignancies, except for the following: Completely resected or eradicated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ, minute/microscopic papillary thyroid carcinoma, minute/microscopic breast cancer, and other malignancies with an extremely low risk of recurrence or metastasis.
• Infectious diseases, including but not limited to: 1) Known Human Immunodeficiency Virus (HIV) infection or Acquired Immunodeficiency Syndrome (AIDS)-related illness; 2) Hepatitis B (HBsAg positive) or Hepatitis C (HCV RNA positive); 3) Active tuberculosis infection, or currently receiving anti-tuberculosis therapy, or having received anti-tuberculosis therapy within 1 year prior to the first dose of study drug; 4) Positive for Treponema pallidum antibody; 5) Other infectious diseases deemed unsuitable for participation in this study by the investigator.
• Previous anti-tumor therapy-related Adverse Events (AEs) that have not resolved to Grade 1.
• Substance abuse (medication or drugs), or clinical, psychological, or social factors that would impair informed consent or study conduct.

Other illness

• Patients with a history of autoimmune disease requiring immunosuppressive medication or hormone therapy (excluding physiological replacement doses).
• History of severe Central Nervous System (CNS) disease, such as grand mal seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, or psychosis.
• Patients with a history of medical treatment for intestinal obstruction, or those with imaging findings during screening indicating intestinal obstruction requiring treatment.
• Patients with moderate to severe cirrhosis (Child-Pugh Class A or worse) and significant portal hypertension.
• Patients with a history of gastrointestinal bleeding within the past 6 months requiring blood transfusion, emergency room observation, or hospitalization.
• Patients with a history of severe intra-abdominal infection.
• History of abdominal surgery within the past 3 months.
• Any uncontrolled active infection.
• Patients with deep vein thrombosis (DVT) or other conditions requiring anticoagulation therapy (e.g., heparin, warfarin).
• Patients with a history of any arterial embolism.
• Patients with a history of severe allergies (e.g., allergies to three or more substances including food, drugs, etc.).
• Any other condition deemed by the investigator to make the subject unsuitable for enrollment.

Lab values

• Patients with a left ventricular ejection fraction (LVEF) \< 50%, severe structural cardiac abnormalities, or arrhythmias requiring medical treatment.
• Presence of other serious conditions prior to apheresis that could potentially limit the subject's participation in this trial, such as: Poorly controlled diabetes (glycated hemoglobin \[HbA1c\] \> 8% despite treatment), inadequately controlled hypertension (blood pressure \> 160 mmHg / 100 mmHg despite medication), myocardial infarction within the last 6 months, severe arrhythmia or unstable angina not well controlled by medication, pulmonary embolism, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), etc.

Other

• Liver metastases occupying more than 30% of the total liver volume.
• Moderate to severe hepatic steatosis (fatty liver).
• Patients with active peptic ulcers.
• Pregnant or lactating women; women or men of childbearing potential planning pregnancy during the study period.
• Presence of moderate or severe ascites.
• Currently participating in another interventional clinical trial.
• Any uncertainty that could affect patient safety or compliance.

• Able to understand and voluntarily sign a written informed consent form.
• Willing and able to comply with the scheduled visit and treatment plan, laboratory tests, and other study requirements.
• Aged ≥ 18 years and ≤ 75 years on the day of signing the informed consent form, male or female.
• ECOG performance status of 0-1.
• Histologically or cytologically confirmed locally unresectable or abdominopelvic metastatic pancreatic ductal adenocarcinoma.
• Pancreatic cancer patients who have failed at least one prior line of therapy or are intolerant to such therapy.
• Medium to high expression of C-MET in pancreatic cancer tissue (defined as ++ or higher, with positive cells \> 25%).
• At least one measurable lesion according to RECIST v1.1 criteria.
• Expected survival ≥ 4 months.
• Adequate organ function as defined by the following laboratory requirements:
  • Note: Subjects must not receive transfusions or growth factor support within 7 days prior to the first dose for hematology assessments.
  • Hematology:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L.
  • Platelet Count (PLT) ≥ 100 × 10⁹/L.
  • Hemoglobin (HGB) ≥ 90 g/L or ≥ 5.6 mmol/L.
  • Liver and Kidney Function:
  • Creatinine (Cr) ≤ 1.5 × ULN.
  • Albumin ≥ 30 g/L (Albumin infusion is not permitted within 14 days prior to the first dose).
  • Total Bilirubin (TBIL) ≤ 1.5 × ULN (For subjects with liver metastases, TBIL ≤ 3 × ULN).
  • Alanine Aminotransferase (ALT) ≤ 2.5 × ULN.
  • Aspartate Aminotransferase (AST): For subjects with liver metastases, ALT and AST ≤ 5 × ULN.
  • Urinalysis:
  • Urine protein ≤ 1+, without accompanying edema or serum albumin levels below the lower limit of normal (LLN).
  • Coagulation:
  • International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; unless the subject is receiving anticoagulant therapy, in which case PT or aPTT must be within the intended therapeutic range of the anticoagulant.
  • Prothrombin Time (PT) must be within the normal range.
• Females of childbearing potential must have a negative serum pregnancy test result within 7 days prior to the first dose and must not be lactating.