This is an interventional study to explore the efficacy and safety of denosumab combined chemotherapy and anti-PD-1/PD-L1 inhibitor in locally advanced or metastatic NSCLC.

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
• Documented negative for EGFR/ALK/ROS1/BRAFV600E/RET/METex14 mutations by validated genomic testing, with no prior targeted therapy and no history of other malignancies
• No previous systemic therapy for advanced/metastatic disease
• At least one measurable lesion per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• No use of parathyroid hormone/derivatives, calcitonin, osteoprotegerin, mithramycin, or potassium supplements within the past 6 months
• Adequate organ and marrow function

Exclusion Criteria:

• Histologically or cytologically confirmed combined small cell and non-small cell lung cancer (mixed histology)
• Any previous systemic anticancer treatment for NSCLC, including chemotherapy, biologics, immunotherapy, or investigational agents
• Prior use of denosumab or any bone-modifying agents (e.g., bisphosphonates)
• Uncontrolled hypocalcemia or hypophosphatemia
• History or current evidence of osteonecrosis of the jaw (ONJ) or osteomyelitis of the jaw