This is a phase I, open-label, single-arm, single-center, dose-escalation study to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of PAN-NeoVax, an artificial intelligence (AI)-designed pan-cancer neoantigen mRNA vaccine delivered via lipid nanoparticles (LNP), administered by intratumoral injection in patients with advanced or metastatic 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 of basic immunization (first 4 doses at weekly intervals, fifth dose at 1 month after the fourth dose).

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 (priority enrollment of advanced head and neck squamous cell carcinoma and malignant melanoma patients)

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 and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements

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 supraventricular or ventricular arrhythmias requiring treatment or intervention
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 requiring no adult intervention; asthma requiring bronchodilator intervention is excluded)
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 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)
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