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 written informed consent prior to the implementation of any trial-relatedprocedures;

• Age ≥ 18 years old and ≤ 80 years old;

• Histologically or cytologically confirmed stage IV NSCLC (International Associationfor the Study of Lung Cancer and American Joint Committee on Cancer Classification 9th Edition TNM Lung Cancer Staging);

• Histologically confirmed bone metastasis, which is assessed by the investigator torequire local radiotherapy treatment;

• Patients who have not undergone systemic drug therapy for lung cancer (includingchemotherapy, targeting, immunotherapy, etc.);

• Adenocarcinoma patients have been confirmed by tumour histology or cytology orhaematology that the driver genes (EGFR, ALK, ROS-1) are all negative, and genetictesting is not required for squamous cell carcinoma patients;

• At least 1 evaluable lesion other than bone metastases (refer to RECIST1.1), andlymph nodes can be used as independent measurable lesions;

• Bone metastases other than the lesions to be radiotherapy do not require localtreatment (surgery or radiotherapy) intervention after evaluation;

• ECOG score 0-1 points;

• Expected survival time > 3 months;

• Adequate organ function, subjects need to meet the following laboratory indicators:

1. In the absence of granulocyte colony-stimulating factor in the past 14 days, theabsolute neutrophil value (ANC) ≥ 1.5x109/L; 2) In the case of no blood transfusionin the past 14 days, platelet ≥ 100×109/L; 3) In the absence of blood transfusion orerythropoietin in the past 14 days, haemoglobin > 9g/dL; 4) Total bilirubin ≤ 1.5times the upper limit of normal (ULN); 5) aspartate aminotransferase (AST) andalanine aminotransferase (ALT) at 2.5 times ULN ≤ (subjects with liver metastasesare allowed ALT or AST ≤5×ULN); 6) serum creatinine ≤ 1.5 times ULN and creatinineclearance (calculated by Cockcroft-Gault formula) ≥ 60 ml/min; 7) good coagulationfunction, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; 8) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within normal limits. If the baseline TSH is outside the normal range,subjects with total T3 (or FT3) and FT4 within the normal range can also beenrolled; 9) Cardiac enzyme spectrum within the normal range (if the investigatorcomprehensively judges that it is not clinically significant, simple laboratoryabnormalities are also allowed to enroll); For female subjects of childbearing age,a urine or serum pregnancy test with a negative result should be received within 3days prior to receiving the first dose of study drug (Cycle 1 Day 1). If the urinepregnancy test cannot be confirmed to be negative, a blood pregnancy test isrequired. Females of non-childbearing potential are defined as at least 1 yearpostmenopausal, or have undergone surgical sterilisation or hysterectomy; If thereis a risk of conception, all participants, male or female, are required to usecontraception with an annual failure rate of less than 1% throughout the treatmentperiod until 120 days after the last dose of study drug (or 180 days after the lastdose of study drug).

Exclusion Criteria:

• The pathology is small cell lung cancer (SCLC), including lung cancer mixed withSCLC 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 notallowed to enroll;

• The radiotherapy lesion to be treated has been treated with radiotherapy or thelesion to be treated cannot be treated with radiotherapy after evaluation;

• Presence of active brain metastases;

• Diagnosis of other malignant diseases other than NSCLC within 5 years before thefirst dose (excluding radically cured basal cell carcinoma of the skin, squamousepithelial carcinoma of the skin, and/or carcinoma in situ after radical resection);

• Current participation in interventional clinical study treatment, or have receivedother investigational drugs or used investigational device treatment within 4 weeksprior to the first dose;

• Prior treatment with the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2drugs or targeting another stimulating or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137) or targeting RANKL (denosumab, nalusolimab);

• Active autoimmune disease requiring systemic therapy (such as use ofdisease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 yearsprior to the first dose. Replacement therapies (e.g., thyroxine, insulin, orphysiologic glucocorticoids for adrenal or pituitary insufficiency) are notconsidered systemic therapy;

• Presence of clinically uncontrollable pleural effusion/ascites effusion (subjectswho do not need to drain the effusion or stop draining for 3 days withoutsignificant increase in effusion can be enrolled);

• Known allogeneic organ transplantation (except corneal transplantation) orallogeneic 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 assintilimab, pemetrexed, nalusopaimab, carboplatin, cisplatin, paclitaxel, etc., ofthe drug in this study;

• Have not recovered adequately from toxicity and/or complications induced by any ofthe 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 1/2antibody positive);

• Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy numberdetected at the same time greater than the upper limit of normal in the laboratorydepartment of the research center);

• Hypocalcemia cannot be improved after treatment;

• Previous or current osteomyelitis or osteonecrosis of the jaw; Dental surgery ororal 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 toenrollment: 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 andsevere symptoms that are difficult to control, such as complete left bundlebranch block, heart block above degree II, ventricular arrhythmia or atrialfibrillation;

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 1year prior to the first dose, or current presence of clinically activeinterstitial 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 chronicactive 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 testvalues that may interfere with the results of the trial, prevent the subjectfrom participating in the study throughout the study, or other conditions thatare considered by the investigator to be unsuitable for enrollment in theopinion of the investigator are not suitable for participation in this study.