At present, the treatment regimen of locally advanced nasopharyngeal carcinoma still needs to be further improved, and the focus of improvement lies in "replacing cisplatin with high-efficiency and low-toxicity treatment regimen". Considering the synergistic effect among radiotherapy, immunotherapy and anti-angiogenesis therapy, we chose PD-1 inhibitor combined with bevacizumab to replace cisplatin chemotherapy.

We plan to use PD-1 inhibitor combined with bevacizumab to replace cisplatin (induction + concurrent ± adjuvant) in patients with locally advanced nasopharyngeal carcinoma. Considering the safety of the original study, we will set up two groups for the adjuvant treatment stage: one group will only use PD-1 inhibitor at the adjuvant treatment stage (low risk group), and the other group will use bevacizumab +PD-1 inhibitor combined treatment (high risk group). Once the efficacy and safety of this protocol are confirmed, it may provide a new treatment option for locally advanced nasopharyngeal carcinoma.

Inclusion Criteria:

1. Voluntary participation with Written informed consent.

2. Age ≥ 18 years and ≤ 65 years.

3. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).

4. Original clinical staged as III-IVa (according to the 8th AJCC edition).

5. Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

7. Patients must have adequate organ function:

   1. White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
   3. Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.
   4. INR, APTT≤1.5 x ULN.

Exclusion Criteria:

1. Subjects with recurrent or metastatic nasopharyngeal carcinoma.
2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
3. Prior therapy with systemic therapy for nasopharyngeal carcinoma.
4. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
5. Prior exposure to antiangiogenic agents.
6. Tumor invasion to the intracranial with clinical symptoms accompanied by cerebral edema, requiring hormone therapy.
7. Any grade ≥2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior to enrollment.
8. Subjects with an active, known or suspected autoimmune disease.
9. Subjects with clinically significant cardiovascular and cerebrovascular diseases.
10. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.
11. Subjects with previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.
12. Subjects with arterial / venous thrombosis events occurred within 6 months of the first dose.
13. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
14. Seropositivity for human immunodeficiency virus (HIV).
15. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).