YMN-A02 for Advanced pMMR Colorectal Cancer With Liver Metastases

Inclusion criteria

• Signed the informed consent form approved by the ethics committee.
• 18-70 years old; ECOG performance status 0-1.
• Histologically or cytologically confirmed colorectal cancer with liver metastases, molecularly classified as pMMR (presence of other distant metastases allowed).
• Patients who have failed or are intolerant to standard therapy, or who refuse standard therapy.

• For patients with RAS/BRAF wild-type and eligible for targeted therapy: enrollment allowed only after disease progression on a prior standard regimen containing anti-EGFR or anti-VEGF monoclonal antibody.
• For patients with BRAF V600E mutation: enrollment allowed only after failure of a prior BRAF inhibitor-containing chemotherapy regimen.
• For patients who do not meet the above molecular characteristics: enrollment allowed only after failure of at least two prior lines of systemic chemotherapy (including a platinum-containing regimen).
• At least one measurable liver metastasis (CT scan long diameter ≥10 mm, slice thickness ≤5 mm).
• Life Expectancy≥3 months.
• Adequate Major Organ Function (all within 14 days before randomization):

• Hemoglobin ≥80 g/L (no transfusion within 14 days); absolute neutrophil count >1.5×10⁹/L; platelet count ≥80×10⁹/L.
• Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN (or ≤5×ULN in the presence of liver metastases); creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
• Left ventricular ejection fraction (LVEF) ≥50%.
• Good compliance, and family agrees to cooperate with survival follow-up.

Exclusion criteria

• Participation in another interventional drug trial within 4 weeks before enrollment.
• Prior or concurrent other malignancy, except: carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, superficial bladder tumor, or any other malignancy that has been curatively treated and recurrence-free for ≥5 years.
• Poorly controlled heart disease or clinical symptoms, including but not limited to: NYHA class ≥2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Pregnant or breastfeeding women.
• Active infection, including but not limited to: active tuberculosis, systemic bacterial or fungal infection (NCI-CTCAE v5.0 grade ≥2), HIV infection, active HBV (HBV DNA >ULN), or active HCV (HCV RNA >ULN).
• History of substance abuse that cannot be abstained from, or history of psychiatric disorders.
• Active or history of autoimmune disease (including but not limited to uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, etc.). Exceptions: vitiligo controlled with only topical agents; childhood asthma completely resolved without any intervention in adulthood. Patients with asthma requiring bronchodilators for medical intervention are excluded.
• Prior vaccination with any mRNA-based drug or mRNA formulation.
• Prior participation in any clinical trial involving lipid nanoparticle (LNP) formulations.
• Contraindications to intravenous infusion.
• History of drug abuse, or any medical, psychological, or social condition (e.g., alcoholism or drug addiction) that, in the investigator's judgment, may affect study compliance.
• Known allergy, hypersensitivity, or intolerance to any component (active substance or excipients) of the study drug; history of severe allergy to drugs, food, or vaccines, including but not limited to anaphylactic shock, angioedema of the larynx, anaphylactic dyspnea, allergic purpura, thrombocytopenic purpura, or Arthus reaction.
• Plan to conceive (either female subject or partner of male subject) from screening through 12 months after the last dose.
• Any concurrent condition that, in the investigator's judgment, may compromise patient safety or interfere with study completion.