Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients

Exclusion Criteria

• •1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer);
• •2. Patients who have received systemic treatment for advanced/metastatic disease especially have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g, CTLA-4, OX 40, CD137);
• •3. Patients concurrently with 19del or 21L858R or other mutation types located in exon 18-21
• •4. Patients who are known to have active brain metastases diagnosed by CT or MRI at the time of screening, however, participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of the study intervention.;
• •5. Patients with severe and/or uncontrolled diseases, such as:
• •(1) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood pressure (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg); (2) Active or uncontrolled serious infection; (3) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; (4) Not completely controlled eye inflammation or eye infection, or any condition that may lead to the above-mentioned ocular diseases (5) Poorly controlled diabetes (fasting blood glucose (FBG) \> 10mmol/L); (6) Routine urine test result indicates that urine protein ≥++, and 24-hour urine protein quantitation is confirmed to be \> 1.0 g; (7) Active tuberculosis, etc.; (8) Uncontrolled hypercalcemia (\> 1.5 mmol/L calcium ion or calcium \> 12 mg/dL or corrected serum calcium \> ULN), or symptomatic hypercalcemia requiring continued diphosphate therapy; (9) Long-term unhealed wounds or fractures; 6. Patients who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders; 7. Patients who are known to have severe allergies (≥ grade 3) to active ingredients and any excipients of pembrolizumab 8. Patients who have other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the investigator to have concomitant diseases that seriously endanger the safety of the patients or affect the patients completing the study.
• •9\. The subjects or their sexual partners cannot or refuse to take effective contraceptive measures during the clinical trial 10. Pregnant or breast-feeding women 11. Patients in other situations who are evaluated by the investigator to be ineligible to be enrolled; 12. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of the study intervention. Administration of killed vaccines is allowed (such as COVID-19 vaccines).
• •13\. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug.
• •14\. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• •15\. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• •16\. Has a known history of Human Immunodeficiency Virus (HIV) infection. 17. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• •18\. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •19\. Has had an allogeneic tissue/solid organ transplant. 20. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
• •21\. Patients who have contraindications of antiangiogenic therapy, including the presence of cavities, and bleeding tendencies judged by the treating physician.