A Prospective, Single-arm, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Tafolecimab and Sintilimab Combined With Chemotherapy in Patients With Advanced or Metastatic Driver Gene-negative Non-small Cell Lung Cancer After Failure of First-line Immunotherapy.

1. Sign a written informed consent before implementing any procedures related to the trial;

2. Age ≥18 years old and ≤75 years old;

3. Life expectancy ≥3 months;

4. Subjects with histologically or cytologically confirmed locally advanced (IIIB-IIIC), metastatic, or recurrent (Stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint American Committee on Cancer Classification 8th Edition TNM Staging of Lung Cancer) relapse or disease progression following multimodal therapy (radiotherapy, surgical resection, or radical chemoradiotherapy for locally advanced disease);

5. Patients must have previously used PD-1 or PD-Ll inhibitors and have disease progression; 1) Participants receiving maintenance therapy (meaning maintenance therapy after an immune checkpoint inhibitor regimen) and who have progressed are eligible for inclusion.

2\) Participants treated with adjuvant, neoadjuvant, or radical chemoradiotherapy containing PD-1 or PD-Ll inhibitors for locally advanced disease and who experienced tumor recurrence or metastasis within 6 months after completion of treatment were eligible for inclusion.

6\. No EGFR, ALK and other mutations; 7. There was at least one radiographically measurable lesion according to the solid tumor efficacy evaluation criteria (RECIST v1.1 edition). Lesions located in the previous radiation field can be considered measurable lesions if progression is demonstrated; 8. Patients with stable brain metastases or whose brain metastases can be controlled were allowed to enroll; 9. ECOG score was 0-1; 10. With sufficient organ function, subjects must meet the following laboratory indicators:

1. Absolute neutrophil count (ANC) ≥1.5x10\^9/L without using granulocyte colony-stimulating factor in the past 14 days;

2. Without blood transfusion in the past 14 days, platelets ≥100×10\^9/L;

3. Hemoglobin \>9g/dL without blood transfusion or erythropoietin use in the past 14 days;

4. Total bilirubin ≤1.5×upper limit of normal (ULN);

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤2.5×ULN (subjects with liver metastases are allowed ALT or AST ≤5×ULN);

6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated using Cockcroft-Gault formula) ≥60 ml/min;

7. Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;

8. Euthyroid, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects can also be enrolled if total T3 (or FT3) and FT4 are within the normal range;

9. Myocardial enzyme spectrum is within the normal range (if the researcher comprehensively judges that simple laboratory abnormalities without clinical significance are also allowed to be included); 11. Female subjects of childbearing potential should undergo a urine or serum pregnancy test with a negative result within 3 days before receiving the first dose of study drug (Day 1 of Cycle 1). If a urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non-reproductive age were defined as at least 1 year postmenopausal, or had undergone surgical sterilization or hysterectomy; 12. If there is a risk of pregnancy, all subjects (regardless of male or female) need to use low annual failure rate during the entire treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of study drug). Contraceptive measures at 1%; 13. Subjects determined by the researcher to meet the admission criteria;

What this study is about