Non-Small Cell Lung Cancer
Conditions
Interventions
one:Tislelizumab,200mg, d1,Q3W,Until progression or intolerable toxicity
one:Pemetrexed,500mg/m2,d1,Q3W,Until progression or intolerable toxicity
one:Carboplatin AUC=5(Max:600mg),d1,Q3W,4 cycles
one:Bevacizumab,7.5mg/kg,d1,Q3W,Until progression or intolerable toxicity
Sponsors
XuanWu Hospital, capital medical university
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease-related inclusion criteria. 1. Patients with locally advanced (stage IIIB/C) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology to be ineligible for radical surgery or radiotherapy based on AJCC 8th edition staging; 2. Patients with EGFR-sensitive mutations: 19del or L858R prior to EGFR-TKI treatment, and patients must provide test results from a certified testing platform; 3. EGFRTKI treatment failure with any of the following requirements; (1) Patients who achieved partial remission or complete remission (according to RECISTver1.1 criteria) after efficacy assessment following treatment with a 1st/2nd generation EGFRTKI (e.g., erlotinib, gefitinib, erlotinib, afatinib, etc.), with subsequent disease progression and proven T790M negativity; (2) Patients who have achieved partial or complete remission (according to RECISTver1.1 criteria) after treatment with a 3rd generation EGFR-TKI (oxitinib or other 3rd generation EGFR-TKI available in China), with subsequent disease progression and confirmed T790M mutation negativity; 4. No other treatment after progression on EGFR-TKI therapy; 5. Have at least one measurable lesion; 6. ECOGPS: 0-1; 7. Life expectancy greater than 3 months; 8. Received stable brain metastases into the group; Hematology, biochemistry and organ function (to be confirmed by test results within 7 days prior to first dose); 9. absolute neutrophil count (ANC) = 1.5x109/L, platelets = 100x109/L, hemoglobin = 90g/L; 10. international normalized ratio (INR) or prothrombin time (PT) = 1.5XULN; 11. serum total bilirubin = 1.5xULN; 12. glutamic oxalyl transaminase (AST) and glutamic alanine transaminase (ALT) = 2.5 x ULN, or if the patient has liver metastases, this criterion is AST and ALT = 5 x ULN; General inclusion criteria. 13. Able to provide written informed consent (ICF) and able to understand and agree to comply with the study requirements and assessment schedule; 14. Male or female aged 18-75 years at the time of signing the ICF; 15. Patients of childbearing potential must be willing to use highly effective contraception for the duration of the study, and for 120 days after the last dose of Tislelizumab.
Exclusion criteria
Exclusion criteria: 1. Patients who have been treated with immune checkpoint inhibitors such as anti-PD-1, PD-L1, or CTLA-4; 2. Patients who have been treated with anti-tumor angiogenic drugs; 3. Patients with symptomatic brain metastases, cancerous meningitis, spinal cord compression, or disease of the brain or soft meninges detected by imaging CT or MRI at screening (patients with brain metastases who have completed treatment 4 weeks prior to enrollment and have stable and non-progressive symptoms may be enrolled, provided they are confirmed to be free of symptoms of brain hemorrhage by cranial MRI, CT or venography evaluation); 4. History of hemoptysis, i.e. coughing up at least one-half teaspoon of fresh blood, within 3 months prior to enrollment; 5. Imaging shows tumor invasion of a large vessel (e.g., pulmonary artery or superior vena cava) that the investigator determines is at risk for hemorrhage; 6. have undergone a minor surgical procedure, such as a tube placement, within 48 hours prior to the first bevacizumab treatment; 7. recent treatment with full-dose oral or parenteral anticoagulants or thrombolytics. Prophylactic use of anticoagulants is allowed; 8. Patients with medical history or test results indicating a genetic predisposition to bleeding or coagulation disorder that may increase the risk of bleeding; 9. Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg); 10. Clinically significant (e.g. active) cardiovascular disease that, in the judgment of the investigator, is intolerant to bevacizumab therapy; 11. Non-healing wounds, active peptic ulcers, or fractures; 12. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or thrombotic disease within 6 months which, in the judgment of the investigator, is intolerant to bevacizumab treatment; 13. Patient with refractory pleural or ascites fluid, such as those requiring puncture drainage within 2 weeks prior to the first dose; 14. Presence or current concurrent other malignancies within the past 2 years, with the exception of cured carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)]; 15. Patients who have not recovered to NCI-CTCAE = grade 1 from antineoplastic therapy-related adverse effects (except alopecia) after prior systemic antineoplastic therapy; 16. Combined with other driver mutations for which there are known drug therapy, untreated with targeted agents. Including but not limited to: ALK gene rearrangement, ROS1 mutation, BRAF600E mutation, MET mutation; 17. Any investigational drug or excipient allergy; 18. Patients with active viral hepatitis requiring treatment as determined by the investigator: a. Chronic hepatitis B virus carriers with HBV DNA = 500 IU/mL (2500 copies/mL) (HBVDNA testing only for patients who test positive for hepatitis B core antibody ); b. Patients who test positive for HCV RNA (HBVDNA testing only for patients who test positive for hepatitis C virus antibody-positive patients for HCV RNA testing). 19. patients with active autoimmune disease or immunodeficiency requiring systemic therapy that the investigator assesses as having an impact on the study treatment; 20. Patients with long-term heavy use of hormones or use of other immunomodulatory agents that the investigator deems to have an impact on study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival;Duration of response;Disease Control Rate;safety; | — |
Countries
China
Contacts
Public ContactYi Zhang
Outcome results
None listed