Non-small cell lung cancer (advanced)
Conditions
Interventions
Experimental group:The nebulized inhalation of the MN-A03 preparation has three dose levels with dose increments
Sponsors
West China Hospital of 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. Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC), staged as IV (any T, any N, M1) according to the AJCC 8th edition TNM staging system, or stage IIIb/IIIc locally advanced unresectable disease not amenable to radical concurrent chemoradiotherapy, or disease progression after radical treatment. 4. Failure of prior standard anti-tumor therapy, with the following specific requirements: (1) Driver-gene positive NSCLC (including EGFR, ALK, ROS1, BRAF V600E, NTRK, MET, RET, KRAS G12C, HER2, etc.): progression after corresponding targeted therapy and failure or intolerance to at least one subsequent systemic therapy. Specifically, for patients with EGFR mutation-positive NSCLC: progression after third-generation EGFR TKIs (including but not limited to osimertinib, almonertinib, furmonertinib, befotertinib, ripretinib, ruiertinib, lietinib) and failure/intolerance to any of the following subsequent systemic therapies: 1) Platinum-based doublet chemotherapy; 2) Platinum-based doublet chemotherapy plus anti-angiogenic therapy; 3) Platinum-based doublet chemotherapy plus immunotherapy; 4) Trop2 ADC monotherapy (e.g., sacituzumab tirumotecan). For patients with ALK fusion-positive NSCLC: progression after at least one ALK-TKI (e.g., crizotinib) and subsequent treatment with next-generation ALK-TKIs (including but not limited to ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, iefinack) or platinum-based doublet chemotherapy. For patients with ROS1 fusion-positive NSCLC: progression after at least one ROS1-TKI (e.g., crizotinib, entrectinib) and subsequent treatment with next-generation ROS1-TKIs (including but not limited to taletrectinib, repotrectinib) or platinum-based doublet chemotherapy. For patients with BRAF V600E mutation: prior treatment with dabrafenib plus trametinib or encorafenib plus binimetinib. For patients with NTRK fusion: prior treatment with larotrectinib, entrectinib or repotrectinib. For patients with MET exon 14 skipping mutation: prior treatment with capmatinib, tepotinib, savolitinib, gumarontinib or bozentinib. For patients with RET fusion: prior treatment with selpercatinib or pralsetinib. For patients with KRAS G12C mutation: prior treatment with sotorasib or adagrasib. For patients with HER2 mutation: prior treatment with trastuzumab deruxtecan or pyrotinib. For other rare driver-gene positive patients: follow the latest NCCN or CSCO guidelines for recommended subsequent therapy. All subsequent treatments must be accompanied by radiographic or clinical evidence of progression, or intolerance. (2) Driver-gene negative NSCLC: progression after at least one line of platinum-based doublet chemotherapy +/- immunotherapy, and failure or intolerance to at least one second-line or later standard regimen recommended by CSCO/NCCN guidelines (e.g., docetaxel, pemetrexed, nivolumab, docetaxel plus ramucirumab, etc.). 5. ECOG performance status 0-1, life expectancy >= 3 months. 6. Pulmonary function: FEV1 >= 50% predicted after bronchodilator, or FEV1/FVC >= 70% and clinically assessed as tolerant to nebulization; no acute exacerbation of severe COPD (GOLD grade 3-4) – patients may be enrolled
Exclusion criteria
Exclusion criteria: 1. Prior receipt of any product targeting the NKG2A or IL-2 pathway. 2. Known hypersensitivity or severe allergic reaction to any component of the study drug. 3. Active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressive therapy (excluding vitiligo, well-controlled type 1 diabetes, and hypothyroidism requiring only hormone replacement therapy). 4. Need for systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days before the first dose. 5. Active or uncontrolled infection, including active tuberculosis (TB), hepatitis B (HBsAg positive with HBV DNA above the lower limit of detection), hepatitis C (HCV antibody positive with HCV RNA positive), or human immunodeficiency virus (HIV) infection. 6. Symptomatic or uncontrolled central nervous system metastases (excluding those that have been treated and stable for >=4 weeks without requiring corticosteroids). 7. Receipt of live vaccine within 4 weeks before the first dose. 8. History of interstitial lung disease or non-infectious pneumonitis (excluding radiation-induced pneumonitis stable for >=6 months). 9. Active hemoptysis (>2.5 mL per episode). 10. Presence of severe underlying organic disease, including: (1) New York Heart Association (NYHA) class III-IV congestive heart failure, unstable angina, myocardial infarction or 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 standard treatment). 11. Presence of uncontrolled pleural effusion, ascites, or pericardial effusion requiring repeated drainage (>=2 times within 4 weeks before enrollment); or bulky tumor (target lesion diameter >=10 cm), extensive bone metastases with severe bone pain or hypercalcemia. 12. Pregnancy or breastfeeding. 13. Participation in another clinical trial with receipt of other investigational drug or device within 3 months before enrollment. 14. Known congenital or acquired severe immunodeficiency (e.g., severe combined immunodeficiency, DiGeorge syndrome, etc.), or prior organ transplantation or allogeneic hematopoietic stem cell transplantation. 15. Mental illness or cognitive impairment that prevents understanding of the informed consent content or compliance with the study procedures. 16. Any other conditions judged by the investigator that may interfere with evaluation of study results, or prevent completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity (DLT);Incidence of adverse events and serious adverse events;Maximum tolerated dose (MTD); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS);Changes in peripheral blood immune cell subsets;Incidence of anti-LNP antibodies;Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab);Changes in cytokine profile;Objective Response Rate(ORR);Overall survival (OS);Duration of response (DoR);Disease control rate (DCR);Best Overall Remission (BOR); | — |
Countries
China
Contacts
Public ContactXuelei Ma
West China Hospital of Sichuan University
Outcome results
None listed