Safety and Tolerability of NCP-IL-22BP mRNA in Advanced Solid Tumors

A Phase I, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Preliminary Anti-Tumor Activity of Non-Cationic Peptide-IL-22BP mRNA (NCP-IL-22BP mRNA) in Patients With Advanced Malignant Solid Tumors

This is a phase I, open-label, single-arm, single-center, dose-escalation study to evaluate the safety, tolerability, and preliminary anti-tumor activity of NCP-IL-22BP mRNA, a non-cationic peptide-delivered mRNA encoding interleukin-22 binding protein (IL-22BP), administered by intratumoral injection in patients with advanced malignant solid tumors who have failed second-line therapy. The study employs a classical "3+3" dose-escalation design with three dose levels (25 μg, 50 μg, and 100 μg mRNA). Each subject will receive 5 doses at weekly intervals. The primary objective is to assess the safety and tolerability of NCP-IL-22BP mRNA, and the secondary objective is to evaluate its preliminary anti-tumor activity.

Inclusion Criteria:

1. Male or female patients aged ≥18 and ≤70 years

2. Histopathologically confirmed advanced recurrent/metastatic malignant solid tumors that have failed second-line therapy with no standard treatment options available (e.g., advanced soft tissue sarcoma, head and neck squamous cell carcinoma, malignant melanoma)

3. ECOG Performance Status score: 0-1

4. Estimated life expectancy ≥3 months

5. At least 28 days since prior chemotherapy, radiotherapy, or surgery

6. At least 6 weeks since prior use of nitrosoureas or mitomycin C

7. Adequate organ function within 14 days prior to enrollment:

   • Hemoglobin ≥90 g/L (no blood transfusion within 14 days)
   • Absolute neutrophil count >1.5×10⁹/L
   • Platelet count ≥80×10⁹/L
   • Total bilirubin ≤1.5×ULN
   • ALT or AST ≤2.5×ULN (≤5×ULN if liver metastases present)
   • Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula)
   • Left ventricular ejection fraction (LVEF) ≥50%

8. Signed written informed consent

Exclusion Criteria:

1. Participation in another clinical drug trial within 4 weeks
2. Tumor located adjacent to major blood vessels or trachea
3. Poorly controlled cardiac conditions: NYHA class >2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant arrhythmias requiring treatment
4. Pregnant or breastfeeding women
5. Active pulmonary tuberculosis, bacterial or fungal infection (≥Grade 2 per NCI-CTCAE v5.0); HIV infection, active HBV or HCV infection
6. History of psychotropic substance abuse that cannot be discontinued, or mental disorders
7. Active autoimmune disease or history of autoimmune disease (exceptions: vitiligo; childhood asthma in complete remission)
8. Currently receiving immunosuppressive therapy
9. History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism, drug addiction)
10. Known allergy, hypersensitivity, or intolerance to IL-22BP or any excipient; history of severe allergic reactions to any drug, food, or vaccine
11. Female subjects with pregnancy plans or male subjects whose partners have pregnancy plans from screening through 12 months after the last dose
12. Any serious concomitant disease that, in the investigator's judgment, would jeopardize patient safety or ability to complete the study