non-small cell lung cancer
Conditions
Interventions
experimental group:Primary lesion: 5 Gy × 3 fractions + Lymph nodes: 2 Gy × 3 fractions ? Toripalimab + platinum-based doublet chemotherapy × 3–4 cycles ? Definitive surgery or radiotherapy +/- chemot
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18–75 years, regardless of gender; 2. Histologically or cytologically confirmed initially unresectable T2-4N2b stage NSCLC according to the AJCC 9th edition staging system (cTNM staging must be confirmed by MDT evaluation based on PET/CT ± EBUS); (1) N2b stage is defined as multistation metastases in mediastinal lymph node stations 4, 5, 6, 7, and 8, with a lymph node SUVmax >2.5 on PET/CT (if 2.5 is lower than the liver SUVmax, the liver SUVmax should be used as the reference); (2) Direct invasion of mediastinal structures such as major vessels, pericardium, nerves, or main trachea in T4 disease must be assessed and confirmed by a radiologist; 3. No known driver gene mutations; 4. ECOG performance status 0–1; 5. Presence of measurable lesions according to RECIST 1.1; 6. Total pulmonary function sufficient to tolerate lung resection as assessed by a surgeon, with FEV1 at least >1.2 and FEV1% >60%; 7. Adequate organ function (within 14 days before enrollment), meeting the following criteria: (1) Hematology: absolute neutrophil count =1.5 × 10?/L, platelet count =100 × 10?/L, hemoglobin =100 g/L; (2) Renal: serum creatinine =1.5 × upper limit of normal (ULN) or creatinine clearance =60 mL/min (calculated using the Cockcroft-Gault formula); (3) Hepatic: total bilirubin =1.5 × ULN, or for subjects with total bilirubin level >1.5 × ULN, direct bilirubin within the normal range; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN; (4) Coagulation: international normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) =1.5 × ULN, except for subjects receiving anticoagulant therapy, provided that PT or aPTT is within the intended therapeutic range of the anticoagulant; 8. Cardiac ejection fraction =49%; 9. Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to the first dose. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use highly effective contraception during the study period and for 180 days after the last dose of study treatment; 10. The subject or legal representative has been informed of the nature of the study, understands the requirements of the protocol, can ensure compliance, and has signed the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to recombinant humanized anti-PD-1 monoclonal antibody drugs or any of their components; 2. History of severe allergic reactions to pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin, or their premedications; 3. Known EGFR sensitizing mutations or ALK positivity; for non-squamous subjects, EGFR and ALK mutation status must be confirmed; 4. Currently participating in and receiving other investigational treatment; 5. Prior systemic therapy for NSCLC, including systemic chemotherapy, targeted therapy, immunotherapy, etc.; 6. History of (non-infectious) pneumonitis/interstitial lung disease that required steroid treatment, or current pneumonitis/interstitial lung disease that requires steroid treatment; 7. Known active tuberculosis; 8. Known active infection requiring systemic treatment; 9. Any known or suspected autoimmune disease or immunodeficiency, except for: subjects with a history of hypothyroidism who do not require hormone therapy or are receiving physiologic doses of hormone replacement therapy; subjects with well-controlled stable type I diabetes mellitus; 10. Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] at screening with detectable HBV-DNA above the upper limit of normal of the study center [subjects with HBV-DNA 5 years) and those expected to achieve curative outcomes after treatment (e.g., adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated with curative intent surgery); 15. Severe cardiovascular disease, New York Heart Association (NYHA) class 2 or higher heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 6 months prior to enrollment; 16. According to the investigator’s judgment, subjects with any history or current evidence of any disease, treatment, or laboratory abnormality that may confound the study results, affect subject compliance, or not be in the best interest of the subject to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1-year event-free survival rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Surgical conversion rate;R0 resection rate;Objective Response Rate;Disease control rate;Pathological complete response rate;The main pathological response rate;Event-free survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactGuowei Che
West China Hospital of Sichuan University
Outcome results
None listed