Advanced pMMR Colorectal Cancer with Liver Metastases
Conditions
Interventions
The 100µg dose group of MN-A02 bifunctional RNA preparation:Enrolled subjects will receive a 100 µg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of
The 250µg dose group of MN-A02 bifunctional RNA preparation:Enrolled subjects will receive a 250 µg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of
The 500µg dose group of MN-A02 bifunctional RNA preparation:Enrolled subjects will receive a 500 µg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of
The 1000µg dose group of MN-A02 bifunctional RNA preparation:Enrolled subjects will receive a 1000 µg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses o
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Informed Consent: Signed the informed consent form approved by the ethics committee 2. Age & Performance Status: 18–70 years old; ECOG performance status 0–1 3. Indication: Histologically or cytologically confirmed colorectal cancer with liver metastases, molecularly classified as pMMR (presence of other distant metastases allowed) 4. Prior Treatment: Patients who have failed or are intolerant to standard therapy, or who refuse standard therapy. (1) 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. (2) For patients with BRAF V600E mutation: enrollment allowed only after failure of a prior BRAF inhibitor-containing chemotherapy regimen. (3) 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) 5. Measurable Lesion: At least one measurable liver metastasis (CT scan long diameter >=10 mm, slice thickness =3 months 7. Adequate Major Organ Function ** (all within 14 days before randomization): (1) Hematology: Hemoglobin >=80 g/L (no transfusion within 14 days); absolute neutrophil count >1.5×10^9/L; platelet count >=80×10^9/L. (2) Biochemistry: Total bilirubin =60 mL/min (Cockcroft-Gault formula). (3) Echocardiography: Left ventricular ejection fraction (LVEF) >=50%. 8. Good compliance, and family agrees to cooperate with survival follow-up
Exclusion criteria
Exclusion criteria: 1. Participation in another interventional drug trial within 4 weeks before enrollment 2. 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 3. 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 4. Pregnant or breastfeeding women 5. 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) 6. History of substance abuse that cannot be abstained from, or history of psychiatric disorders 7. 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 8. Prior vaccination with any mRNA-based drug or mRNA formulation 9. Prior participation in any clinical trial involving lipid nanoparticle (LNP) formulations 10. Contraindications to intravenous infusion 11. 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 12. 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 13. Plan to conceive (either female subject or partner of male subject) from screening through 12 months after the last dose 14. Any concurrent condition that, in the investigator’s judgment, may compromise patient safety or interfere with study completion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Dose-Limiting Toxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS);Objective Response Rate (ORR); | — |
Countries
China
Contacts
Public ContactPeng Xingchen
West China Hospital of Sichuan University
Outcome results
None listed