an exploratory study of tislelizumab in combination with chemotherapy in immuno-experienced patients with egfr/alk/ros1-negative advanced nsclc in the second-line setting

Conditions: Lung Cancer

Summary: the goal of this clinical trial is to explore the efficacy and safety of denosumab in combination with tislelizumab and chemotherapy in the second-line treatment of immuno-experienced patients with egfr/alk/ros1-negative advanced nsclc. primary endpoint: progression-free survival (pfs) assessed by investigators according to recist 1.1; secondary endpoint: 1. overall survival (os) assessed by investigators according to recist 1.1; 2. objective response rate (orr) assessed by investigators according to recist 1.1; 3. disease control rate (dcr) assessed by investigators according to recist 1.1; 4. duration of response (dor) assessed by investigators according to recist 1.1; exploratory endpoint: bone metastasis-free survival. participants will receive denosumab combined with tislelizumab and docetaxel.


Eligibility criteria:
inclusion criteria: 1. age≥ 18 years old; 2. patients with histologically or cytologically confirmed non-bone metastases stage iv nsclc; 3. egfr, alk, and ros1 are all wild-type (for other driver genes, if there is no first-line approval for corresponding targeted therapy or if the patient refuses targeted therapy, these patients are allowed to be enrolled); 4. first-line treatment with immune checkpoint inhibitors and clinical benefit (pfs ≥ 3 months); 5. have measurable lesions (according to recist 1.1 criteria, the long diameter of ct scan of tumor lesions is ≥10mm, the short diameter of ct scan of lymph node lesions is ≥15mm, and the thickness of the scanning layer is not more than 5mm, and the measurable lesions have not received local treatment such as radiotherapy and cryotherapy); 6. ecog ps: 0-2 points; 7. estimated survival time≥ 3 months; 8. adequate hematologic function, defined as absolute neutrophil count ≥1.5×109/l, platelet count ≥ 80×109/l, hemoglobin ≥ 90g/l (no history of blood transfusion within 7 days, not corrected with g-csf and other hematopoietic stimulating factors); 9. adequate liver function, defined as total bilirubin levels ≤1.5 times the upper limit of normal (uln) and aspartate aminotransferase (ast) and alanine aminotransferase (alt) levels ≤ 2.5 times uln, or for patients with liver metastases, ast and alt levels ≤ 5 times uln; 10. adequate renal function, defined as creatinine clearance ≥50ml/min (cockcroft-gault formula); 11. adequate coagulation function, defined as the international normalized ratio (inr) or prothrombin time (pt) ≤ 1.5 times uln; 12. for female subjects of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days prior to receiving the first dose of study drug, and if the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required; 13. if there is a risk of conception, male and female patients need to use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue until at least 180 days after stopping the trial treatment (note: abstinence can be accepted as a contraceptive method if abstinence is the subject's usual lifestyle and preferred contraceptive method); 14. subjects voluntarily joined this study, signed a written informed consent form before the implementation of any trial-related procedures, had good compliance, and cooperated with follow-up. exclusion criteria: 1. patients on first-line docetaxel chemotherapy; 2. patients with symptomatic brain metastases (symptoms of brain metastases remain clinically stable for at least 1 month after treatment, and no steroids and anticonvulsants can be enrolled for at least 1 month before entering the study); 3. presence of clinically uncontrollable pleural effusion/ascites effusion (patients who do not need to drain the effusion or who have stopped draining for 3 days without a significant increase in effusion can be enrolled); 4. have not recovered adequately from toxicity and/or complications caused by any intervention (i.e., ≤ grade 1 or to baseline, excluding fatigue or alopecia, prior to initiation of treatment); 5. diagnosis of other malignant tumors within 5 years before the first dose, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ that has undergone radical resection, if other malignant tumors or lung cancer are diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent metastatic lesions is required; 6. active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and peritoneal metastasis requiring clinical intervention; 7. received solid organ or blood system transplantation; 8. class iii-iv congestive heart failure (new york heart association classification), poorly controlled and clinically significant arrhythmia; 9. active autoimmune disease requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are not considered systemic therapy; 10. patients who need long-term systemic use of corticosteroids (patients who need intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroids due to copd and asthma can be enrolled); 11. history of non-infectious pneumonitis requiring corticosteroid treatment within 1 year before the first dose; 12. have an active infection requiring treatment or have used systemic anti-infective drugs within one week before the first dose; 13. known psychiatric illness or substance abuse that may affect compliance with trial requirements; 14. those who are considered unsuitable for inclusion by the investigator.