IMP3-saRNA Vaccine in Advanced NSCLC

Inclusion Criteria: 1. Patients aged at least 18 years at screening who voluntarily sign an ethics committee-approved informed consent form before any study procedure and agree to participate in this study. 2. Patients with histologically or cytologically confirmed non-small cell lung cancer who have failed standard treatment, are intolerant to standard treatment, or have refused standard treatment, and whose tumor tissue is positive for IMP3 expression. The IMP3 pathological test result must be issued by the pathology department of this hospital or by a qualified pathology institution recognized by the study center. If a previous pathology report cannot confirm IMP3 status, IMP3 testing must be performed during screening, and only patients with positive results may be enrolled. Note: 1. Patients with EGFR-sensitive mutations must have failed third-line or later treatment, including failure of at least one EGFR-TKI. 2. Patients with ALK-positive disease must have failed third-line or later treatment, including failure of at least one ALK inhibitor. 3. Patients with ROS1-positive disease must have failed third-line or later treatment, including failure of at least one ROS1 inhibitor. 4. Patients with EGFR wild-type disease and no ALK or ROS1 positivity must have failed second-line or later treatment, including platinum-containing treatment. 3. At least one measurable or evaluable lesion according to RECIST version 1.1. 4. Eastern Cooperative Oncology Group performance status score of 0 to 2. 5. Estimated life expectancy of at least 3 months. 6. Adequate major organ function, with the following test results meeting the requirements within 7 days before treatment: 1. Hemoglobin ≥80 g/L without blood transfusion within 14 days; absolute neutrophil count \>1.5 × 10\^9/L; white blood cell count ≥3.0 × 10\^9/L; platelet count ≥80 × 10\^9/L. 2. Total bilirubin ≤1.5 × upper limit of normal; alanine aminotransferase or aspartate aminotransferase ≤2.5 × upper limit of normal; in patients with liver metastasis, alanine aminotransferase or aspartate aminotransferase ≤5 × upper limit of normal. 3. Serum creatinine ≤1.5 × upper limit of normal or creatinine clearance estimated by the Cockcroft-Gault formula ≥60 mL/min. 4. Prothrombin time and international normalized ratio ≤1.5 × upper limit of normal, unless the patient is receiving warfarin anticoagulation. 5. Cardiac function: left ventricular ejection fraction ≥50%; QTcF interval ≤450 ms. 7. Male patients with reproductive potential and female patients of childbearing potential voluntarily agree to use effective contraception, such as condoms, intrauterine devices, or spermicides, from signing the informed consent form until 6 months after completion of vaccination. Oral contraceptives are not allowed. Female cancer patients must have a negative pregnancy test and agree not to breastfeed during the study and for at least 18 months after administration of the investigational vaccine. 8. The washout period for previous antitumor therapy must be no less than 4 weeks, and the washout period for molecular targeted therapy must be no less than 5 half-lives. Palliative radiotherapy must have been completed for at least 2 weeks; thoracic radiotherapy must have been completed for at least 3 months; and major surgery must have been completed with at least 4 weeks of recovery. Exclusion Criteria: 1. Patients with a history of other malignancies, except for malignancies considered eligible by the investigator, such as cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or intramucosal gastrointestinal carcinoma without recurrence within 5 years before screening. 2. Any uncontrolled clinical disease, such as respiratory, circulatory, digestive, neurologic, hematologic, genitourinary, or endocrine disease, or psychiatric disease, such as depression or schizophrenia, or other major disease that, in the investigator's judgment, may interfere with provision of informed consent, interfere with interpretation of study results, pose a risk to the participant by participating in this study, or otherwise affect achievement of the study objectives. 3. Any active autoimmune disease or history of autoimmune disease, including but not limited to immune-related neurologic disease, multiple sclerosis, autoimmune demyelinating neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis, or Stevens-Johnson syndrome, except type 1 diabetes mellitus controlled with a stable dose of insulin. Participants with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be enrolled; participants with asthma requiring medical intervention with bronchodilators are not eligible. 4. Patients with active central nervous system metastases, including but not limited to carcinomatous meningitis and spinal cord compression, must be excluded. However, patients with metastatic central nervous system tumors may participate in this study if they have recovered to baseline for at least 2 weeks before enrollment, with no residual signs or symptoms related to central nervous system treatment. In addition, patients must have discontinued corticosteroids for 4 weeks. 5. Allergy to the study drug, including any excipients. History of severe allergy to any drug, food, or vaccination, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, or local allergic necrotic reaction, such as Arthus reaction. 6. Contraindications to injection: a. inflammation, trauma, or ulceration at the injection site; b. severe bleeding or coagulation tendency, or marked decrease in platelets or coagulation factors; c. any abnormality or permanent body art, such as a tattoo, at the vaccination site that, in the investigator's judgment, may interfere with observation of local reactions at the vaccination site. 7. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation. 8. Prior antitumor therapeutic vaccine or cellular immunotherapy. 9. Participation in another drug or device clinical trial within 4 weeks before screening. 10. Major surgery within 4 weeks before the first vaccination, except for minor procedures such as catheter placement or protocol-required biopsy; or insufficient resolution of the effects of surgery or trauma for at least 14 days before enrollment. 11. Participants who have received systemic treatment with corticosteroids at a dose \>10 mg/day prednisone or an equivalent dose of another glucocorticoid, or other immunosuppressive agents, within 14 days before the first vaccination. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal hormone replacement therapy at a dose ≤10 mg/day prednisone equivalent are allowed. 12. Any toxicity caused by previous antitumor therapy has not recovered to grade ≤1 according to NCI CTCAE version 5.0 before the first administration of the study drug, except for alopecia of any grade and grade 2 neuropathy related to prior platinum therapy. 13. Known hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or syphilis infection, or positive screening test for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus antibody, HIV antibody, or Treponema pallidum antibody: HBsAg positivity or HBcAb positivity with HBV DNA quantitative test result ≥500 IU/mL or ≥2000 copies/mL, or meeting the lower limit of positivity at the study center; HCVAb positivity with HCV RNA ≥ the upper limit of normal at the study center. 14. Active tuberculosis, history of active tuberculosis, or severe acute or chronic infection requiring systemic treatment. Patients suspected of having active tuberculosis must undergo chest X-ray, sputum testing, and exclusion by clinical symptoms and signs. Patients with objective evidence of previous or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severe impairment of pulmonary function are excluded. 15. History of drug abuse or known medical, psychological, or social conditions, such as alcoholism or drug addiction. 16. Pregnant or breastfeeding women, or female participants who plan to become pregnant or male participants whose partners plan to become pregnant from screening until 12 months after completion of all study drug injections. 17. Receipt of any vaccine within 30 days before vaccination with the study vaccine, or planned receipt of any vaccine other than the study vaccine during the study. 18. History of deep vein thrombosis or pulmonary embolism within 6 months before enrollment. 19. Uncontrolled fungal, bacterial, viral, or other infection requiring antibiotic treatment. Simple urinary tract infection or uncomplicated bacterial pharyngitis may be allowed after consultation with the medical monitor. 20. History or presence of central nervous system disease, such as seizure disorder, cerebral ischemia or hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system. 21. Significant immunodeficiency. 22. Negative tumor tissue IMP3 pathological test result or inability to obtain or confirm IMP3 status. 23. Any other factor that, in the investigator's judgment, makes the participant unsuitable for this study, or any disease that may interfere with safety or efficacy evaluation of the study treatment. 24. Participants who are unwilling or unable to comply with study requirements.