The Efficacy and Safety of Narlumosbart in Combination With Stereotactic Body Radiation Therapy to Improve the Efficacy of First-line Chemotherapy Combined With Immunotherapy in Patients With Bone Metastases From Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

* Signed informed consent prior to the implementation of any trial-related procedures;
* Age 18-80 years old;
* Histologically or cytologically confirmed stage IV NSCLC according to the TNM Classification of Malignant Tumours, 9th edition；
* Histologically confirmed bone metastases requiring local radiotherapy；
* Patients who have not undergone systemic drug therapy for lung cancer (including chemotherapy, targeting, immunotherapy, etc.);
* Driver genes (EGFR, ALK, ROS-1) negative in adenocarcinoma patients (genetic testing not required for squamous cell carcinoma) ;
* At least one evaluable non-bone lesion (refer to RECIST1.1);
* Bone metastases other than the lesions to be radiotherapy do not require local treatment (surgery or radiotherapy) intervention after evaluation;
* ECOG score 0-1 points;
* Expected survival time \> 3 months;
* Adequate organ function, defined as meeting all of the following laboratory criteria within 14 days prior to enrollment: 1) ANC ≥1.5×10⁹/L (no G-CSF); 2) Platelets ≥100×10⁹/L (no transfusion); 3) Haemoglobin ≥9 g/dL (no transfusion/EPO); 4) Bilirubin ≤1.5×ULN; 5) AST/ALT ≤2.5×ULN (≤5×ULN if liver metastases); 6) Creatinine ≤1.5×ULN or CrCl ≥60 mL/min; 7) INR/PT ≤1.5×ULN; 8) TSH within normal limits (or FT3/FT4 normal if TSH abnormal); 9) Cardiac enzymes (troponin I, CK-MB) ≤ ULN (isolated abnormalities not clinically significant are permitted).

Exclusion Criteria:

* The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC;
* The lesion is an isolated lesion and can be treated radically;
* Patients who need surgical treatment after the evaluation of the study are not allowed to enroll;
* The radiotherapy lesion to be treated has been treated with radiotherapy or the lesion to be treated cannot be treated with radiotherapy after evaluation;
* Presence of active brain metastases;
* Other malignancies within 5 years (except cured non-melanoma skin cancer or carcinoma in situ);
* Prior treatment with anti-PD-1, anti-PD-L1, or RANKL-targeting agents;
* Active autoimmune disease requiring systemic therapy;
* Presence of clinically uncontrollable pleural effusion/ascites effusion (subjects who do not need to drain the effusion or stop draining for 3 days without significant increase in effusion can be enrolled);
* Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
* Presence of active bone metabolism disease (Paget bone disease, Cushing's syndrome, and hyperprolactinemia), rheumatoid arthritis, uncontrolled hyper/hypothyroidism, hyperparathyroidism/hypoparathyroidism;
* Those who are known to be allergic to the active ingredients or excipients such as sintilimab, pemetrexed, nalusopaimab, carboplatin, cisplatin, paclitaxel, etc., of the drug in this study;
* Have not recovered adequately from toxicity and/or complications induced by any of the interventions (i.e., ≤ grade 1 or to baseline, excluding fatigue or alopecia, prior to initiation of treatment);
* Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive);
* Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected at the same time greater than the upper limit of normal in the laboratory department of the research center);
* Hypocalcemia cannot be improved after treatment;
* Previous or current osteomyelitis or osteonecrosis of the jaw; Dental surgery or oral surgery that does not heal; Acute dental or jaw disease requiring oral surgery; Those who plan to undergo invasive dental surgery during the study;
* Use of any of the following anti-bone metabolizing agents within 6 months prior to enrollment: Parathyroid hormone (PTH) or derivatives; Calcitonin; Osteoprotein; Vaccination with a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1);
* Pregnant or lactating women;
* Presence of any serious or uncontrollable systemic disease, such as:

  1. Resting ECG has major abnormalities in rhythm, conduction or morphology and severe symptoms that are difficult to control, such as complete left bundle branch block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;
  2. unstable angina, congestive heart failure, New York Heart Association (NYHA) classification ≥ grade 2 chronic heart failure;
  3. myocardial infarction within 6 months prior to enrollment;
  4. unsatisfactory blood pressure control;
  5. History of non-infectious pneumonitis requiring glucocorticoid therapy within 1 year prior to the first dose, or current presence of clinically active interstitial lung disease;
  6. active tuberculosis;
  7. Presence of active or uncontrolled infection requiring systemic therapy;
  8. Presence of clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;
  9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
  10. poorly controlled diabetes mellitus (fasting blood glucose (FBG) \>10mmol/L);
  11. Those whose urine routine showed a urine protein ≥++, and confirmed that the 24-hour urine protein was \> 1.0 g;
  12. Subjects with mental disorders who are unable to cooperate with treatment; Medical history or evidence of disease, abnormal treatment or laboratory test values that may interfere with the results of the trial, prevent the subject from participating in the study throughout the study, or other conditions that are considered by the investigator to be unsuitable for enrollment in the opinion of the investigator are not suitable for participation in this study.