Narlumosbart

A Phase II, single-arm, single-centre clinical trial to evaluate the efficacy and safety of nalusobasumab in combination with stereotactic radiosurgery to improve the efficacy of first-line chemotherapy combined with immunotherapy in patients with bone metastases from advanced non-small cell luncancer.Purpose:1.To assess the effectiveness of nalusomab in combination with SBRT and first-line chemotherapy and immunotherapy for bone metastases in lung cancer; 2.To assess the safety of nalusolimab in combination with SBRT and first-line chemotherapy and immunotherapy for bone metastases in lung cancer.Primary Endpoint:To assess the objective response rate of non-radiotherapy lesions in patients with bone metastases from stereotactic radiosurgeryplus nalusolimab and first-line chemotherapy and immunotherapy driver gene negative patients with advanced non-small cell lung cancer bone metastases.Secondary Endpoints:1. To evaluate the safety and tolerability of combination treatment regimens: including the incidence of adverse events and serious adverse events, and the incidence of treatment discontinuation due to AEs/SAEs;2. Assess the subject's progression-free survival according to RECIST v1.1;3. To assess the overall survival of the subjects;4. Incidence of bone-related events at different time points, including 3 months, 6 months, 12 months;5. To explore the changes from baseline in pain scoreand quality of life score during nalmaxolbaimab treatment; Study design：Patients with advanced bone metastases who have not received any prior systemic therapy for non-small cell lung cancer will receive first-line treatment with nalusolimab and bone target lesion SBRT plus conventional dose immune checkpoint inhibitors and chemotherapy after screening eligible subjects who meet the enrolment conditions to sign informed consent, including nalproxolimab 120 mg/time, subcutaneous injection, administered every 4 weeks. For the treatment of SBRT for bone metastases, the dose of 24 Gy/3 F is used for spinal metastases, and 30 Gy/5 F or 35 Gy/5 F is used for non-spinal lesions. Chemotherapy combined with immune checkpoint inhibitor therapy was used in accordance with the guidelines until progression, loss to follow-up, intolerable toxicity, and withdrawal of informed consent by the subject .Subjects eligible for inclusion in this study must meet all of the following criteria:1. Signed written informed consent prior to the implementation of any trial-related procedures;2. Age ≥ 18 years old and ≤ 80 years old;3. Histologically or cytologically confirmed stage IV NSCLC ;4. Histologically confirmed bone metastasis, which is assessed by the investigator to require local radiotherapy treatment;5. Patients who have not undergone systemic drug therapy for lung cancer ;6. Adenocarcinoma patients have been confirmed by tumour histology or cytology or haematology that the driver genes ( ALK, ROS-1) are all negative, and genetic testing is not required for squamous cell carcinoma patients;7. At least 1 evaluable lesion other than bone metastases , and lymph nodes can be used as independent measurable lesions;8. Bone metastases other than the lesions to be radiotherapy do not require local treatment intervention after evaluation;9. ECOG score 0-1 points;10. Expected survival time > 3 months;11. 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, the absolute neutrophil value (ANC) ≥ 1.5x109/L;2) In the case of no blood transfusion in the past 14 days, platelet ≥ 100×109/L;3) In the absence of blood transfusion or erythropoietin in the past 14 days, hemoglobin > 9g/dL;4) Total bilirubin ≤ 1.5 times the upper limit of normal 5) aspartate aminotransferase and alanine aminotransferase at 2.5 times ULN ;6) serum creatinine ≤ 1.5 times ULN and creatinine clearance ≥ 60 ml/min;7) good coagulation function, defined as international normalized ratio or prothrombin time (PT) ≤ 1.5 times ULN;;1. Statistical assumptions and sample size calculations According to Huiping Qiang et al., the ORR of patients with bone metastases was 25.0% for patients with bone metastases treated with immunotherapy and 71.4% for patients with bone metastases based on immunotherapy combined with immunotherapy and combined therapy for bone metastases according to Huiping Qiang et al.. Here, H0 is taken as 25%, assuming that H1 expects ORR to reach 50%, and unilateral α=0.05 and power=0.8 are used, 9 patients are enrolled in the first stage, if ≥ 2 patients achieve CR/PR, the second stage of enrollment will be performed, and if only only 2 patients < achieve CR/PR, the trial will be terminated. In the second phase, 15 patient were enrolled, and a total of 24 patients were enrolled, and a total of 27 subjects were enrolled in this project, considering the dropout rate of the first 10% of the study evaluation.