YMN-A02 for Advanced pMMR Colorectal Cancer With Liver Metastases

Prior treatment

• 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.
• Prior vaccination with any mRNA-based drug or mRNA formulation.
• Prior participation in any clinical trial involving lipid nanoparticle (LNP) formulations.
• Any concurrent condition that, in the investigator's judgment, may compromise patient safety or interfere with study completion.

Other illness

• 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.
• 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.
• 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.

Lab values

• 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).

Other

• Pregnant or breastfeeding women.
• Contraindications to intravenous infusion.
• Plan to conceive (either female subject or partner of male subject) from screening through 12 months after the last dose.

• 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.