A Dose-Expansion Trial of Intravenous HNF4α srRNA for Unresectable or Metastatic Colorectal Cancer

Exclusion Criteria

• •1. Patients who have completed standard adjuvant chemotherapy after tumor resection and relapsed or developed metastasis after a drug-free interval of 6 months, and have not received standard systemic therapy.
• •2. Patients with tumor tissue testing confirming mismatch repair deficiency or high microsatellite instability (dMMR/MSI-H) who have not received immune checkpoint inhibitor treatment (PD-1 monoclonal antibody or PD-L1 monoclonal antibody).
• •3. Patients with clinical or radiological evidence of current intestinal obstruction, perforation, or bleeding; or patients assessed by the investigator to be at high risk of perforation or bleeding.
• •4. Serum albumin \< 28 g/L, or bilirubin \> 3×ULN, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \> 5×ULN.
• •5. Patients with significant renal impairment, serum creatinine \> 1.5×ULN, or creatinine clearance \< 40 mL/min; urine protein \<2+ (if urine protein ≥2+, a 24-hour urine protein quantification is required, and patients with 24-hour urine protein quantification \<1 g may be eligible).
• •6. Absolute neutrophil count \< 1.5×10\^9/L, or platelets \< 50×10\^9/L, or hemoglobin \< 9 g/dL.
• •7. International Normalized Ratio (INR) \> 2.
• •8. Patients with known brain metastases from tumors.
• •9. Patients with uncontrolled hypertension, diabetes, or other severe cardiac or pulmonary diseases, or severe organ dysfunction.
• •10. Patients who have received local or systemic anti-tumor treatments (including immunotherapy, targeted therapy, or chemotherapy) within 4 weeks, or radiotherapy within 3 weeks, except for treatment regimens assessed as disease progression according to RECIST (version 1.1) criteria.
• •11. Patients with adverse events related to previous local or systemic anti-tumor treatments still ≥ Grade 2 (excluding alopecia and other events deemed tolerable by the investigator).
• •12. Patients with uncontrollable active infections (e.g., pulmonary or abdominal infections).
• •13. Patients with malignancies other than colorectal cancer within the past 5 years, with the exception of low-risk malignancies with a low risk of metastasis or death (estimated 5-year overall survival \> 90%), such as early gastrointestinal cancer treated effectively, cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, etc.
• •14. Patients with active autoimmune diseases requiring systemic therapy within the past 2 years, or autoimmune diseases judged by the investigator to have a potential for recurrence or planned treatment, including but not limited to inflammatory bowel disease, celiac disease, Wegener's granulomatosis, Hashimoto's thyroiditis, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis.
• •15. Patients who require systemic treatment with corticosteroids (prednisone or equivalent \> 10 mg/day) or other immunosuppressive drugs within 14 days before the first dose of the investigational drug.
• •16. Patients who are preparing for or have previously undergone allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• •17. Patients who are positive for HBV-DNA or HCV RNA.
• •18. Patients with known active tuberculosis. Patients suspected of having active tuberculosis must be excluded based on chest imaging, sputum tests, and clinical symptoms and signs.
• •19. Patients who are positive for human immunodeficiency virus (HIV).
• •20. Pregnant or breastfeeding women, or women who cannot rule out the possibility of pregnancy.
• •21. Patients who have participated in other drug trials within the past 4 weeks.
• •22. Other situations deemed by the investigator as unsuitable for participation in this clinical trial.