Locally advanced or metastatic recurrent non - squamous NSCLC with EGFR - sensitive mutations and high PD - L1 expression (CPS = 25%).
Conditions
Interventions
Experimental group:The combination of Limertinib and bevacizumab.
Control Group:Limertinib
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: To be eligible for this study, subjects had to meet all of the following criteria: 1. Provided written informed consent before performing any trial-related procedures; 2. Age>=18 years old; 3. Non-squamous non-small cell lung cancer confirmed by histology or cytology; 4. According to the International Association for the Study of Lung Cancer and the American Joint Committee on Classification of Cancer 9th edition TNM stage of lung cancer, locally advanced (IIIB-IIIC), metastatic or recurrent (stage IV) patients are not suitable for treatment by surgery or radiotherapy; 5. The presence of EGFR sensitive mutations (Ex19del, L858R) confirmed by tumor histology or cytology or hematology; 6. PD-L1 expression CPS>=25%; 7. ECOG score 0-1; 8. No previous anti-angiogenesis inhibitor or EGFR-TKI therapy; 9. At least one radiographic measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version v1.1. Lesions within the previous irradiation field could be considered measurable if progression was confirmed. 10. Subjects with asymptomatic or symptomatic stable brain metastases after local treatment were allowed to participate as long as they met the following conditions: 1) measurable lesions outside the central nervous system 2) no central nervous system symptoms or worsening of symptoms for at least 2 weeks 3) no need for glucocorticoid therapy, glucocorticoids discontinued within 7 days before the first dose, or glucocorticoids that were stable and reduced to less than 10mg per day of prednisone (or the equivalent) within 7 days before the first dose. 11. Expected survival time >3 months; 12. Adequate organ function was defined as: 1) absolute neutrophil count (ANC) >=1.5x10^9/L without granulocyte colony-stimulating factor administration for the last 14 days; 2) platelet count >=100×10^9/L without blood transfusion in the past 14 days; 3) hemoglobin >9g/dL in the absence of blood transfusion or erythropoietin use in the past 14 days; 4) Total bilirubin =60 ml/min; 7) good coagulation function, defined as INR or PT <=1.5 times ULN; 8) Euthyroid, defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH was beyond the normal range, the subjects could be included if the total T3 (or FT3) and FT4 were within the normal range. 9) Myocardial enzymes within the normal range (simple laboratory abnormalities that were judged by the investigators as not clinically significant were also allowed); 13. For women 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 (day 1 of cycle 1). If a urine pregnancy test result could not be confirmed as negative, a blood pregnancy test was requested. Women who were not of reproductive age were defined as those who had been postmenopausal for at least 1 year or had undergone surgical sterilization or hysterectomy. 14. If there was a risk of pregnancy, all subjects (male or female) were required to use contraception with an annual failure rate of less than 1% for the entire treatment period until 120 days (or 180 days) after the last dose of study drug.
Exclusion criteria
Exclusion criteria: Subjects who met the following criteria were not eligible for inclusion in the study: 1. Small cell lung cancer (SCLC), including SCLC and NSCLC mixed lung cancer; 2. Patients had received any EGFR-TKI therapy or anti-angiogenic therapy; 3. Received the following treatments: 1) received systemic anti-tumor therapy within 3 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine for anti-tumor indications), etc.; 2) received any investigational drug within 4 weeks before treatment; 3) receipt of high-dose immunosuppressive drugs (systemic corticosteroids more than 10mg/ day of prednisone or its equivalent) within 4 weeks before treatment; 4) received a live attenuated vaccine within 4 weeks before treatment (or planned to receive a live attenuated vaccine during the study); 5) major surgery (such as open thoracotomy, thoracotomy, or Capf) or unhealed surgical wounds, ulcers, or fractures within 4 weeks before treatment. 4. Patients with clinically uncontrollable pleural effusion/peritoneal effusion (patients who did not require drainage or had no significant increase in effusion after 3 days of cessation of drainage could be enrolled); 5. Patients who received thoracic radiotherapy of more than 30Gy within 6 months prior to treatment or palliative radiotherapy of 30Gy or less within 7 days prior to treatment (palliative radiotherapy for bone or intracranial lesions was allowed); 6. Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) were not considered systemic therapy; 7. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 8. Known to be allergic to the active ingredients or excipients of bevacizumab and riertinib; 9. Has not fully recovered from any intervention-related toxicity and/or complications before starting treatment (i.e., grade <=1 or baseline, excluding fatigue or alopecia); 10. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive); 11. Untreated active hepatitis B (defined as both HBsAg positivity and HBV-DNA copies greater than the upper limit of normal in the laboratory at the participating center); Note: Subjects with hepatitis B who met the following criteria were also eligible for inclusion: 1) Subjects with HBV viral load <1000 copies /ml (200 IU/ml) before the first dose should receive anti-HBV therapy throughout the study drug treatment to avoid viral reactivation. 2) For subjects with anti-HBc (+), HBsAg (-), anti-hbs (-) and HBV viral load (-), Prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is required 12. Active HCV-infected subjects (HCV-antibody positive and HCV-RNA level above the lower limit of detection); 13. A live vaccine dose within 30 days before the first dose (cycle 1, day 1); Note: Administration of injectable inactivated virus vaccine against seasonal influenza within 30 days before the first dose is allowed; Live, attenuated, intranasal influenza vaccine was not allowed. 14. Pregnant or lactating women; 15. The presence of any serious or uncontrolled systemic disease, such as: 1) significant rhythm, conduction or morphological abnormalities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Safety;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactTianqing Chu
Shanghai Chest Hospital
Outcome results
None listed