SRT Combined With Envafolimab and Endostar in the First-line Treatment of Advanced NSCLC

This is a prospective, single-arm phase II clinical study. It intends to evaluate the efficacy and safety of stereotactic radiation therapy (SRT) combined with envafolimab and endostar as first-line treatment in stage IV non-small cell lung cancer (NSCLC) patients without actionable EGFR/ALK/ROS1 driver gene alterations and with PD-L1 TPS ≥ 1%. A total of 61 eligible participants will receive combination treatment of stereotactic radiotherapy, envafolimab and endostar. Tumor response will be evaluated every 6 weeks according to RECIST v1.1, and treatment-related adverse events will be monitored based on NCI-CTCAE v5.0. The treatment will continue until disease progression, patient withdrawal, loss of follow-up or death.

Inclusion Criteria: 1. Subjects voluntarily participate in this study, sign the written informed consent form, and demonstrate good compliance. 2. Aged 18-80 years old at the time of signing informed consent, male or female. 3. Histologically confirmed stage IV non-small-cell lung cancer (NSCLC) according to the 8th IASLC/AJCC TNM staging system, with negative actionable driver gene alterations (EGFR/ALK/ROS1), and no prior systemic anti-cancer treatment. 4. Provide archived tumor tissue samples or newly obtained core/excisional biopsy specimens from tumor lesions which have not received prior anti-tumor therapy or radiotherapy. Formalin-fixed paraffin-embedded (FFPE) tissue blocks are preferred over slides; newly-obtained biopsy samples are preferred over archived tissues. PD-L1 expression ≥1% is confirmed by immunohistochemistry. For subjects without newly-obtained tissue, 5-8 slices of 3-5 μm paraffin sections of archived tissue collected within 2 years before enrollment are acceptable. 5. Have at least one radiologically measurable lesion per RECIST version 1.1: target lesion with longest diameter ≥10 mm on CT/MRI, or pathologically enlarged lymph node with short-axis diameter ≥15 mm on CT scan. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Expected survival time ≥ 3 months. 8. Treatment-naive patients without previous systemic anti-tumor therapy (including radiotherapy, chemotherapy, targeted or immunotherapy), or patients with disease recurrence more than 6 months after completion of postoperative adjuvant chemotherapy. 9. Adequate organ and bone marrow function confirmed by laboratory tests obtained within 7 days before enrollment. No blood product transfusion, growth factors, albumin or other corrective medications are permitted within 14 days prior to laboratory assessment: 1\) Hematology: absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥75×10⁹/L, hemoglobin (HGB) ≥90 g/L (no transfusion or erythropoietin-dependency within 14 days); 2) Liver function: total bilirubin (TBIL) ≤2×ULN; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5×ULN; serum albumin ≥28 g/L; alkaline phosphatase (ALP) ≤5×ULN; 3) Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min using Cockcroft-Gault formula; urine protein \