A Study of Chidamide Combined With Ivonescimab in the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) With Acquired Resistance to Immunotherapy and High Yes-associated Protein (YAP) Expression

Inclusion criteria

• ✓. 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;