Safety and Tolerability of AI-Designed Pan-Cancer Neoantigen mRNA Vaccine (PAN-NeoVax) in Advanced Solid Tumors

Inclusion criteria

• Male or female patients aged ≥18 and ≤70 years
• Histopathologically confirmed advanced recurrent/metastatic malignant solid tumors that have failed second-line therapy with no standard treatment options available (priority enrollment of advanced head and neck squamous cell carcinoma and malignant melanoma patients)
• ECOG Performance Status score: 0-1
• Estimated life expectancy ≥3 months
• At least 28 days since prior chemotherapy, radiotherapy, or surgery
• At least 6 weeks since prior use of nitrosoureas or mitomycin C
• 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%
• Signed written informed consent and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements

Exclusion criteria

• Participation in another clinical drug trial within 4 weeks
• Tumor located adjacent to major blood vessels or trachea
• Poorly controlled cardiac conditions: NYHA class >2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention
• Pregnant or breastfeeding women
• Active pulmonary tuberculosis, bacterial or fungal infection (≥Grade 2 per NCI-CTCAE v5.0); HIV infection, active HBV or HCV infection
• History of psychotropic substance abuse that cannot be discontinued, or mental disorders
• Active autoimmune disease or history of autoimmune disease (exceptions: vitiligo; childhood asthma in complete remission requiring no adult intervention; asthma requiring bronchodilator intervention is excluded)
• Currently receiving immunosuppressive therapy
• History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism, drug addiction)
• Known allergy, hypersensitivity, or intolerance to PAN-NeoVax or any excipient; history of severe allergic reactions to any drug, food, or vaccine (including anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, Arthus reaction)
• Female subjects with pregnancy plans or male subjects whose partners have pregnancy plans from screening through 12 months after the last dose
• Any serious concomitant disease that, in the investigator's judgment, would jeopardize patient safety or ability to complete the study