Tislelizumab Combined With Tofacitinib and Docetaxel for NSCLC After Failure of First-Line Immunotherapy

Tofacitinib is a pan-target JAK inhibitor that blocks the activation of immune cells by inhibiting the JAK1/2/3 signaling pathways. When used in combination with immune checkpoint inhibitors, it has the potential to enhance anti-tumor efficacy. This study aims to evaluate the efficacy and safety of Tislelizumab combined with Tofacitinib and Docetaxel in patients with locally advanced or metastatic NSCLC who have failed first-line immunotherapy. Additionally, the study seeks to explore potential genomic and immunological biomarkers of therapeutic response in the second-line treatment setting, providing a basis for subsequent research.

Inclusion Criteria: * Patients with non-small cell lung cancer (NSCLC) confirmed through pathological histological examination. * Adenocarcinoma patients must be verified to lack driver gene mutations such as EGFR, ALK, ROS1, etc.; squamous carcinoma patients are exempt from this requirement. * In accordance with the 8th edition of the TNM staging classification of lung cancer by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification, patients with histologically or cytologically confirmed locally advanced (stage IIIB/C) or metastatic (stage IV) NSCLC who are ineligible for surgical intervention or radical concurrent chemoradiotherapy. * Subjects who have previously received one PD-1/L1 inhibitor ± one platinum-based double-drug chemotherapy (either combined or sequential, with the sequence being inconsequential) and have demonstrated clinical benefit (PFS ≥ 84 days) following PD-1/L1 inhibitor treatment (with or without chemotherapy) before experiencing disease progression. * According to RECIST1.1 criteria, subjects must possess at least one radiologically measurable lesion. Tumor baseline radiological assessment should be conducted within 28 days prior to the initiation of medication. * Age range: 18 to 75 years. * ECOG performance status score of 0-1. * Normal function of major organs. * Women of childbearing potential must employ appropriate contraceptive measures from screening until 3 months post-study treatment cessation and must refrain from breastfeeding. * Patients must voluntarily participate in the study, sign informed consent, and demonstrate good compliance. Exclusion Criteria: * Patients with prior exposure to JAK inhibitors. * Patients with active interstitial lung disease. * Presence of other active malignant tumors requiring concurrent treatment. Previous use of anti-tumor traditional Chinese medicine. * Evidence of severe or uncontrolled systemic diseases. * Clinically significant active infection. * Resting ECG showing clinically significant major abnormalities in rhythm, conduction, or morphology. * Myocardial infarction, coronary artery/peripheral artery bypass, or cerebrovascular accident within the past 3 months. * Insufficient bone marrow reserve or organ function. * Pregnant, breastfeeding, or planning to become pregnant during the study period. * Previously or currently suffering from clinically active interstitial lung disease. * History of hypersensitivity to any active or inactive components of tislelizumab/tofacitinib or to drugs with similar chemical structure or same category as tislelizumab/tofacitinib. * Any severe or uncontrolled eye disease.