Lung cancer
Conditions
Interventions
Treatment group:This study adopts a "3+3" dose escalation design with 3 dose levels. Dose level 1 (DL1) : 2×10^10 per time, dose level 2 (DL2) : 4×10^10 per time, dose level 3 (DL3) : 8×10^10 per time
if it needs to be completed on the same day, it is recommended to administer YMN-M12 first and then implement the standard treatment of the cycle. If it cannot be completed on the same day due to actu
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, understand and comply with the requirements of the study protocol, and be able to complete all visits, examinations and treatment procedures on schedule. 2. Aged 18-75 years, regardless of gender. 3. Patients with primary non-small cell lung cancer (NSCLC) confirmed by histopathology or cytopathology; classified as Stage IV (any T, any N, M1) or Stage IIIb/IIIc locally advanced unresectable disease according to the 8th edition of the AJCC TNM staging system, who are ineligible for curative concurrent chemoradiotherapy, or have experienced disease progression after curative treatment. 4. Positive IMP3 protein expression in tumor tissues confirmed by immunohistochemistry (IHC) testing (definition: the 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. Patients with advanced NSCLC who have experienced disease progression, recurrence or intolerance after prior first-line standard anti-tumor therapy, and are judged by the investigator to be suitable for second-line standard anti-tumor treatment. Specific requirements are as follows: (1) Driver gene-positive NSCLC (EGFR/ALK/ROS1, etc.): disease progression, recurrence or intolerance after first-line standard treatment matched to molecular typing, and eligible for second-line standard anti-tumor therapy as assessed by the investigator; (2) Driver gene-negative NSCLC: disease progression, recurrence or intolerance after prior first-line standard systemic anti-tumor therapy, and suitable for second-line standard anti-tumor treatment as judged by the investigator. 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 7 days prior to enrollment): (1) Blood routine: absolute neutrophil count (ANC) >= 1.5×10^9/L, platelet (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. Negative serum pregnancy test for women of childbearing potential before enrollment; all subjects of childbearing potential (male and female) agree to adopt medically recognized effective contraceptive measures during the study period and for 6 months after study completion. 9. Able to provide adequate archived or fresh tumor tissue specimens for IMP3 expression detection and subsequent biomarker analysis.
Exclusion criteria
Exclusion criteria: 1. Patients with a clear history of allergy to Ad5 adenovirus vector, vaccine excipients, IL-12-related drugs, or previous 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., severe nasal septum deviation); 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 active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune pneumonia/hepatitis/enteritis, etc.), or autoimmune diseases requiring systemic immunosuppressant/glucocorticoid treatment within the past 2 years; patients using inhaled/topical glucocorticoids or thyroid hormone replacement therapy are excluded. 5. Patients with active interstitial lung disease, pulmonary fibrosis confirmed by chest imaging, or a history of non-infectious pneumonia requiring systemic hormone therapy. 6. Patients with symptomatic central nervous system (CNS) metastasis, carcinomatous meningitis, or CNS metastasis requiring hormone/dehydration therapy to control intracranial symptoms; asymptomatic and stable CNS metastasis (>= 4 weeks after local treatment, no radiological progression, and no need for hormone therapy) is 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) NYHA Class III-IV congestive heart failure, unstable angina, myocardial infarction/stroke within 6 months before enrollment, and severe uncontrolled arrhythmia; (2) Decompensated liver cirrhosis, chronic renal failure requiring regular dialysis; (3) Uncontrolled severe hypertension or diabetes (poorly controlled despite standardized treatment). 9. Patients who have received systemic glucocorticoids (prednisone equivalent dose >= 10 mg/day) or other immunosuppressants within 2 weeks before enrollment; inhaled/topical glucocorticoids and hormone antiemetic treatment are excluded. 10. Patients with uncontrolled pleural effusion, ascites or pericardial effusion requiring repeated puncture and drainage (>= 2 drainage procedures within 4 weeks before enrollment); or patients with massive tumors (maximum diameter of target lesion >= 10 cm), extensive bone metastasis accompanied by severe bone pain or hypercalcemia. 11. Pregnant or lactating women. 12. Patients who have participated in other clinical trials and received other investigational drugs/devices within 3 months before enrollment. 13. Patients with known congenital or acquired severe immunodeficiency diseases (such as severe combined immunodeficiency, DiGeorge syndrome, etc.), or with a history of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Dose limiting toxicity, DLT;Vital signs, physical examination and local tolerance; | — |
Secondary
| Measure | Time frame |
|---|---|
| Preliminary effectiveness testing;Specific immune response;Vehicle shedding/discharge monitoring;Immunogenicity tests;Cytokines/pharmacodynamic indicators;Evaluation of imaging efficacy;Tumor efficacy indicators(This includes preliminary efficacy indicators such as objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).); | — |
Countries
China
Contacts
Public ContactXuelei Ma
West China Hospital, Sichuan University
Outcome results
None listed