lung cancer
Conditions
Interventions
Treatment group:This study adopts a 3+3 dose-escalation design with 3 dose levels established:
Dose Level 1 (DL1): 2 × 10^1? viral particles per dose
Dose Level 2 (DL2): 4 × 10^1? viral particles per
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the written informed consent form, be able to understand and comply with the requirements of the study protocol, and complete all visits, examinations and treatment procedures on time. 2. Age 18-75 years, both genders. 3. Patients with histologically or cytologically confirmed malignant tumors at an advanced stage, with evidence of pulmonary metastasis confirmed by imaging and/or pathology; subjects must have at least one measurable or evaluable pulmonary metastatic lesion. 4. Positive IMP3 protein expression in tumor tissues confirmed by immunohistochemistry (IHC) testing (definition: proportion of IHC-positive tumor cells >=5%; for samples with unclear IHC results, borderline expression, or as prespecified in the study, further supplementary verification by FISH is allowed). 5. Failure, intolerance, or lack of available standard effective treatment as judged by the investigator after prior standard anti-tumor therapy. Specific requirements are as follows: (1) For malignant tumors with a clear standard treatment pathway, disease progression should have occurred after at least the corresponding standard systemic therapy; (2) For tumors with targetable driver genes or molecular markers, disease progression after completing the corresponding standard targeted therapy, or intolerance to standard targeted therapy; (3) For patients who have previously received immunotherapy, chemotherapy, targeted therapy, endocrine therapy, or other standard treatments, there must be clear evidence of treatment failure or disease progression; (4) For patients who, in the investigator's judgment, have no expected benefit from standard therapy or are unsuitable to continue receiving existing standard treatment, enrollment may be considered after thorough evaluation. 6. ECOG performance status score of 0-1, with an estimated survival time >=3 months. 7. Baseline laboratory tests meet the following organ function criteria (tests conducted within =1.5×10^9/L, platelet count (PLT) >=100×10^9/L, hemoglobin (Hb) >=90 g/L; (2) Liver function: AST/ALT =50 mL/min (calculated by the Cockcroft-Gault formula); (4) Coagulation function: INR <=1.5, APTT <=1.5×ULN. 8. Women of childbearing potential must have a negative serum pregnancy test before enrollment; all men and women of childbearing potential agree to use medically recognized effective contraceptive measures during the study period and for 6 months after study completion. 9. Ability to provide sufficient archived or fresh tumor tissue specimens for IMP3 expression detection and subsequent biomarker analysis; specimens may be derived from primary or metastatic lesions.
Exclusion criteria
Exclusion criteria: 1. Patients with a clear history of allergy to Ad5 adenovirus vector, vaccine excipients, or IL-12-related drugs, or those who have previously experienced severe hypersensitivity reactions to similar biological agents. 2. Patients with nasal/sinus diseases or anatomical abnormalities that may affect the safety, tolerability, or mucosal absorption of intranasal administration, including but not limited to: severe rhinitis (including severe allergic rhinitis), active sinusitis, nasal polyps, severe atrophic rhinitis, recurrent epistaxis, nasal malignant tumors, obvious nasal structural abnormalities (e.g., significant deviation of the nasal septum), those who have undergone nasal or sinus surgery within 3 months before screening, or other conditions deemed unsuitable for intranasal administration by the investigator. 3. Patients with prior receipt of IMP3-targeted anti-tumor therapy, Ad5 vector vaccine treatment, or recombinant IL-12-related drug therapy. 4. Patients with a history of active autoimmune disease (such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune pneumonia/hepatitis/enteritis, etc.), or autoimmune disease requiring systemic immunosuppressants/glucocorticoids within the past 2 years; patients using inhaled/topical glucocorticoids or thyroid hormone replacement therapy are excluded. 5. Patients with active interstitial lung disease or pulmonary fibrosis confirmed by chest imaging, or a history of non-infectious pneumonia that previously required systemic hormone therapy. 6. Patients with symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or CNS metastases requiring hormone/dehydration therapy to control intracranial symptoms; patients with asymptomatic, stable CNS metastases (>=4 weeks after local treatment, no radiological progression, and no need for hormone therapy) are excluded. 7. Patients with active infections, including: (1) Bacterial, fungal, or viral infections requiring intravenous anti-infective treatment; (2) Active tuberculosis; (3) HBsAg positive with HBV DNA above the lower limit of detection (without standardized antiviral treatment); (4) HCV RNA positive; (5) HIV antibody positive. 8. Patients with severe underlying organic diseases, including: (1) New York Heart Association (NYHA) class III-IV congestive heart failure, unstable angina, myocardial infarction/stroke within 6 months before enrollment, or severe uncontrolled arrhythmia; (2) Decompensated liver cirrhosis or chronic renal failure requiring regular dialysis; (3) Uncontrolled severe hypertension or diabetes mellitus (failing to achieve target despite standardized treatment). 9. Patients who have received systemic glucocorticoids (prednisone equivalent dose >=10 mg/day) or other immunosuppressants within 2 weeks before enrollment; patients using inhaled/topical glucocorticoids or hormone antiemetic therapy are excluded. 10. Patients with pulmonary conditions that significantly affect safety evaluation or study execution, including: (1) Uncontrolled pulmonary infection; (2) Significant hypoxemia or requirement for continuous oxygen support; (3) Extensive pulmonary metastases resulting in severe respiratory impairment; (4) Uncontrolled pleural effusion, or requiring repeated puncture and drainage (>=2 times within 4 weeks before enrollment); (5) Significant airway compression, atelectasis, or other conditions judged by the investigator to po
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Dose-limiting toxicity (DLT);Adverse events and serious adverse events;Vital signs, physical examination and local tolerance;Mucosal immune indicators; | — |
Secondary
| Measure | Time frame |
|---|---|
| Preliminary effectiveness testing;Specific immune response;Vehicle shedding/discharge monitoring;Immunogenicity tests;Cytokines/pharmacodynamic indicators; | — |
Countries
China
Contacts
Public ContactXuelei Ma
West China Hospital, Sichuan University
Outcome results
None listed