non-small-cell lung cancer
Conditions
Interventions
Experimental Group:All patients will be treated with tislelizumab (200 mg intravenously every 3 weeks for up to 2 years) in combination with sitravatinib(70 mg once daily orally for up to 2 years) and
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Disease-Related Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC who are not candidates for radical surgery or radiotherapy. 2. No known EGFR mutation, ALK rearrangement or ROS1 rearrangement. 3. Radiological progression as defined by RECIST V1.1 after previous treatment with an anti-PD -(L)1 antibody in locally advanced or metastatic NSCLC included progression with anti-PD -(L)1 antibody plus platinum-based chemotherapy or progression with platinum-based chemotherapy after anti-PD -(L)1 antibody monotherapy. 4. At least 1 measurable lesion per RECIST v1.1 as determined by the investigator. 5. Eastern Cooperative Oncology Group performance status (ECOG PS) = 1. Hematology, biochemistry and organ function: 6. Patients must have adequate organ function as evidenced by the following laboratory values = 7 days before the first dose: (1) Patients did not require blood transfusion or growth factor support for 14 days (including 14 days) prior to blood collection during the screening period: Absolute Neutrophil Count (ANC) >= 1.5×10^9/L, Platelet count =80×10^9/L, Hemoglobin >= 90g/L. (2) Serum Creatinine = 1.5 × upper limit of normal (ULN), or estimated glomerular filtration rate (GFR) = 60 mL/min/1.73m^2 by Chronic Kidney Disease Epidemiology Collaboration equation. (3) Urine protein1.5 x ULN, alkaline phosphatase should be = 2.5 x ULN. (5) Serum total bilirubin = 1 × ULN. (6) International normalized ratio (INR) = 1.5 × ULN or prothrombin time (PT) = 1.5 × ULN. (7) Activated partial thromboplastin time (aPTT) = 1.5 x ULN. General Inclusion Criteria: 7. Ability to provide written informed consent and understand and agree to comply with the requirements and assessment plan of the study. 8. Be >= 18 and <= 75 years of age at the time of signing the informed consent form. 9. Patients of childbearing potential must be willing to use highly effective methods of birth control for the duration of the study and for 180 days after the last dose of tislelizumab.
Exclusion criteria
Exclusion criteria: Disease-Related Exclusion Criteria: 1.Previous treatment with docetaxel. 2.Received prior anti-angiogenic drug therapy (including but not limited to bevacizumab, anti-VEGFR TKI such as anlotinib, lenvatinib, apatinib). 3.Previously received immunotherapy other than anti-PD- (L) 1 antibody, including but not limited to anti-CTLA-4, anti-TIGIT, anti-OX40, and anti-CD137. 4.Toxicities caused by prior anti-tumor therapy have not yet returned to baseline or stabilized (except for adverse events unlikely to pose a safety risk, such as alopecia, neuropathy, or specific laboratory abnormalities). 5.Unacceptable toxicity following prior anti-PD- (L) 1 antibody therapy as defined below: a.= Grade 3 AEs related to anti-PD-1/PD-L1 therapy that are refractory to standard of care and require treatment discontinuation. b. Grade =2 irAE associated with anti-PD -(L)1 antibody therapy, unless the AE has recovered or been well controlled after suspension of anti-PD -(L)1 antibody therapy and/or steroid therapy, except for previous colitis, encephalitis, myocarditis, hepatitis, uveitis, and pulmonary inflammation. c.Any grade central nervous system (CNS) or ocular AE associated with anti-PD- (L) 1 antibody. Note: Patients with prior endocrine AEs may be allowed a first dose of study drug if they remain stable and asymptomatic after appropriate replacement therapy. 6.Meningeal metastases due to metastatic NSCLC or the presence of active brain metastases. Note: Patients who were stable at screening were eligible only if they met all of the following criteria: a. Brain imaging at screening showed no evidence of immediate progression, clinical stability for at least 2 weeks, and no evidence of new brain metastases; b. Measurable lesions and/or evaluable disease other than the CNS; c. Currently corticosteroid-free for CNS disease; steroids were discontinued 3 days prior to first dose of study drugs; stable doses of anticonvulsants were allowed; d. No stereotactic radiotherapy or whole brain radiotherapy within 14 days before the first dose of study drugs. 7. Poorly controlled pleural effusion, pericardial effusion or ascites requiring frequent drainage (recurrence = 14 days after intervention). 8. Patients with spinal cord compression caused by metastatic disease that has not been radically treated with surgery and/or radiotherapy, or patients with spinal cord compression that has been previously diagnosed and treated without evidence of clinically stable disease for>2 weeks before the first dose of study drug. 9. Patients who have received any Chinese herbal or Chinese patent medicine for cancer control within 14 days before the first dose of the study drug.Study Drug-Related Exclusion Criteria: 10. NSCLC with hemoptysis (> 50 mL/d). 11. Central cavity or imaging examination showed that the tumor was adjacent to important vascular structures, or the investigator considered that the patient's tumor might invade important vessels and may lead to fatal bleeding. 12. Patients who have used anticoagulants (such as warfarin or similar agents) requiring therapeutic INR monitoring within 6 months before the first dose of study drugs, which may affect the treatment in the judgment of the investigator. 13.Patients with active bleeding disease, = Grade 3 (per NCI-CTCAE v5.0) any bleeding event, unhealed wound, ulcer, or bone fracture within 4 weeks prior to the first dose of study drug. 14. Patients with a history of arterial/deep vein thrombosis w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 6-month progression free survival rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Objective response rate;Disease control rate;Duration of response;Overall survival;Safety of treatment;potential biomarkers; | — |
Countries
China
Contacts
Public ContactWeimin Li
West China Hospital of Sichuan University
Outcome results
None listed