• Aged 18-85 years.

• ECOG score was 0-2.

• Histological or cytological diagnosis confirmed non-small cell lung cancer, which was staged IIIB-IV according to AJCC version 8.

• Patients have received first-line chemotherapy combined with ICIs (PD1/PD-L1, ICIs type is not limited) and developed drug resistance.

• Normal function of major organs, that is, meeting the following criteria: a) blood routine examination (hematopoietic growth factors and blood transfusion were not used within 7 days): granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 80 g/L; b) biochemical examination: total bilirubin ≤ 1.5 × ULN (upper limit of normal); serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula); c) coagulation function: INR or PT ≤ 1.5 × ULN (upper limit of normal), if the subject is receiving anticoagulant therapy, as long as PT is in the range proposed by anticoagulant drugs; d) urine routine examination: urine routine examination urine protein ≥ 2 +, 24-hour urine protein quantitative examination should be performed, such as quantitative urine protein ≤ 1 g/24 h.

• Female subjects of childbearing age or male subjects with sexual partners of childbearing age should take effective contraceptive measures throughout the treatment period and 6 months before and after the treatment period.

• Subjects voluntarily participate in the study and sign the informed consent form