Non-Small Cell Lung Cancer (NSCLC) Clinical Trials

• Written informed consent must be signed before implementing any trial-related procedures;

• Age ≥18 years old;

• Have histologically or cytologically confirmed locally advanced (IIIB/IIIC stage), metastatic or recurrent (IV stage) non-small cell lung cancer (NSCLC) that is not operable and not suitable for radical concurrent chemoradiotherapy, as classified by the 9th edition of the TNM staging system of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer;

• Previously received first-line PD-1/PD-L1 inhibitor monotherapy or combination therapy, with a progression-free survival (PFS) of ≥ 6 months under the initial PD-1/PD-L1-containing treatment regimen;

• Previously received only first-line systemic treatment;

• Able to provide 15 pieces of biopsied tumor tissue or tumor tissue sections after PD-1/PD-L1 treatment resistance, pathologically confirmed as non-small cell lung cancer, and centrally laboratory-confirmed high YAP protein expression. Eligible subjects voluntarily provide 5-15 sections of tumor tissue samples from initial diagnosis. (YAP immunohistochemical staining intensity is graded as 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong); the proportion of positive tumor cells is graded as 0 (0-5%), 1+ (6-25%), 2+ (26-50%), 3+ (51-75%), and 4+ (\>75%). The YAP IHC score is calculated by multiplying the staining intensity by the proportion of positive tumor cells: YAP IRS = Staining Intensity (A) × Proportion of Positive Tumor Cells (B). A YAP IHC score \< 6 indicates low YAP expression, and ≥ 6 indicates high YAP expression);

• Asymptomatic brain metastasis patients are eligible for enrollment;

• Palliative radiotherapy completed within 2 weeks before study enrollment is allowed, and radiotherapy-related toxicity has recovered to ≤ Grade 1 (CTCAE 5.0). Radiated lesions are not considered evaluable lesions unless there is evidence of progression after radiotherapy;

• No prior use of any traditional Chinese medicine (TCM) with anti-tumor effects, or prior use of TCM with anti-tumor effects no more than 3 times (one dose counts as one time), and discontinuation of such TCM for ≥ 2 weeks before the start of study drug treatment.

• Patients must meet the following laboratory test requirements at screening:

⁃ Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L without the use of growth factors in the past 14 days;

⁃ Platelet count ≥ 80 × 10⁹/L and hemoglobin ≥ 80 g/L without blood transfusion in the past 14 days;

⁃ Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × Upper Limit of Normal (ULN) (patients with liver metastasis are allowed to have ALT or AST ≤ 5 × ULN);

⁃ Total bilirubin ≤ 1.5 × ULN (patients with liver metastasis or biliary obstructive tumors are allowed to have ≤ 2.5 × ULN);

⁃ Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by the Cockcroft-Gault formula) ≥ 45 ml/min;

⁃ ECOG performance status score of 0-1;

⁃ Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN;

⁃ Expected survival time \> 12 weeks;

⁃ Negative pregnancy test (applicable only to women of childbearing potential).