This single-center, open-label, phaseⅠstudy is to evaluate the efficacy of Tislelizumab in combination with Bevacizumab and Pemetrexed for the first-line treatment of advanced Non-squamous Non-small Cell lung cancer in Elderly Patients

Patients received Bevacizumab, 7.5mg/kg d1, Pemetrexed, 500mg/m2, d1 and Tislelizumab 200mg, d4, Q3W, for 4 cycles; then Tislelizumab 200mg, d1 Q3w and Bevacizumab 7.5mg/kg d1 Q3W, maintenance treatment for 2 years.

Inclusion Criteria:

Subjects who must meet all the following criteria should be selected:

1. Agree to participate in this trial and sign written informed consent form.
2. Male or female, age ≥ 65 years.
3. Expected survival time ≥ 3 months and able to be followed-up.
4. Stage IIIB/IIIC/IV non-squamous NSCLC patients without previous systemic therapy (according to AJCC8th) or patients with stage IIIB/IIIC/IV non-squamous NSCLC who have relapsed after surgery (if adjuvant therapy was administered, more than 6 months of drug discontinuation is required).
5. Without EGFR mutation and ALK and ROS1 fusion genes.
6. Patients can not receive concurrent chemoradiothrapy after multidisciplinary consultation and discussion.
7. At least one measurable tumor indicator along with a lesion with a maximum diameter of ≥ 1 cm (diagnosed by imaging, e.g., CT, MRI, ECT).
8. ECOG PS 0-1 within 7 days before enrollment.
9. Within 14 days prior to the start of treatment, laboratory results of routine blood, liver and kidney function and hormone levels meet the following criteria: platelets (PLT) ≥ 100 × 109/L, neutrophils (ANC) ≥ 1.5 × 109/L, hemoglobin (HGB) ≥ 90 g/L, aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN for liver metastases), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, and alanine aminotransferase (ALT) ≤ 1.5 × ULN. × ULN), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, serum creatinine (CR) ≤ 1.25 × ULN; cortisol and thyroid function are in the normal range.
10. Toxic effects of prior chemotherapy have resolved to grade 1 or less (except alopecia). Subjects must have recovered from toxicity or complications of these interventions if they have received major surgical treatment or > 30Gy of radiation therapy, i.e., they are still eligible for enrollment after 6 months.

Exclusion Criteria:

Subjects who meet any of the following criteria could not participate in this study:

1. Received bevacizumab and/or pemetrexed within 6 months prior to the first dose of study drug.
2. Other malignant tumors with disease progression or requiring aggressive treatment within 5 years of enrollment. Exceptions included early-stage tumors (carcinoma in situ or stage I tumors) that received radical treatment, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast that received potentially radical treatment.
3. Have had an allogeneic tissue/organ transplant.
4. Participating or have participated in investigational drug therapy within 4 weeks prior to the first dose of the trial.
5. Receiving systemic hormone therapy or are receiving any other form of immunosuppressive therapy (except docetaxel pretreated glucocorticoids) within 14 days prior to the first dose of the experimental treatment.
6. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or major surgical procedure within 1 month prior to the first use of study drug; received chest radiation therapy greater than 30 Gy within 6 months prior to the first use of study drug; received chest radiation therapy at 30 Gy or less within 1 month prior to the first use of study drug.
7. Prior treatment with other PD-1 antibodies and other immunotherapy targeting PD-1/PD-L1.
8. Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressants) within the past 2 years Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic therapy.
9. Having congenital or acquired immune deficiency (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥ 2.5 x 10^3 copies/ml), or hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection for the assay).
10. Patients who have received live vaccine within 4 weeks prior to the first administration of study drug are permitted to receive inactivated viral vaccine for seasonal influenza, administered by injection, but not live attenuated influenza vaccine administered via the nose.
11. Patients with known active central nervous system (CNS) metastases and/or cancerous meningitis. Subjects who have had treatment for brain metastases may also participate in this study provided that the subject is stable (no evidence of progression for at least 4 weeks and all neurological symptoms have returned to baseline levels as determined by MRI prior to the first dose), has no evidence of new or expanding brain metastases, and has not used hormone therapy for at least 3 days prior to study dosing.
12. Bleeding tendency, high bleeding risk, or coagulopathy with a history of thrombotic disease within 6 months and/or hemoptysis within 3 months; being treated with full doses of oral and/or parenteral anticoagulants and thrombolytics (prophylactic anticoagulation is allowed); having used aspirin or other non-steroidal anti-inflammatory drugs that inhibit platelet function within 10 days; and CT/MRI imaging showing tumor encapsulation or invasion of the lumen of large blood vessels.
13. Poorly controlled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) and patients with prior hypertensive crisis and hypertensive encephalopathy; severe cerebrovascular disease.
14. Non-healing wounds, peptic ulcers in active phase, tracheo-esophageal fistulas, gastrointestinal perforations and intra-abdominal abscesses within 6 months.
15. Have an active infection that requires systemic treatment via Intravenous injection.
16. Have mental illness or other condition, such as uncontrolled heart or lung disease, diabetes mellitus, etc., that prevents cooperation with study treatment and monitoring requirements.
17. History of interstitial lung disease.
18. Patients with moderate to heavy smoking need to quit smoking for more than 1 month.
19. Known allergy to any of the components of the study drug.
20. Patients who are regular users of any drug (including "recreational" use) or have recent history (within 1 year) of substance abuse (including alcohol) when signing the informed consent form.
21. Poor compliance and inability to cooperate with the clinical study.