Inclusion Criteria:
1. Age ≥18 and ≤65 years at diagnosis, regardless of sex.
2. Previously untreated nasopharyngeal carcinoma histologically confirmed as non-keratinizing carcinoma according to the World Health Organization (WHO) classification.
3. Locoregionally advanced nasopharyngeal carcinoma classified as stage II or III, excluding T3N0-1 disease, according to the 9th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) clinical staging system.
4. Eastern Cooperative Oncology Group performance score of 0-1.
5. Adequate marrow function: white blood cell count \> 4 × 10⁹/L hemoglobin \>90g/L and platelet count \>100×10⁹/L
6. Adequate hepatic and renal function：
* Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
* Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN
* Alkaline phosphatase ≤ 2.5 × ULN
* clearance rate ≥ 60 ml/min
7. Other laboratory and clinical criteria
* Normal thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG)
* For patients aged \>50 years with a history of smoking, normal pulmonary function test (PFT) results are required
* For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any exclusion criteria listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits
8. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.
9. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug (e.g., condoms, physician-guided regular use of oral contraceptives).
10. Positive plasma Epstein-Barr virus (EBV) DNA before initiation of treatment (\> 0 copies/mL).
Exclusion Criteria:
1. Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \>1×10\^3 copies/mL, positive for anti-hepatitis C virus (HCV) antibody , positive for anti-hepatitis C virus (HCV) antibody
2. Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
3. Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received confirmed and regular anti-tuberculosis treatment.
4. Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
5. History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
6. Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone \>10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
7. Uncontrolled cardiac conditions, such as:
* Heart failure with New York Heart Association (NYHA) classification ≥ Class II;
* Unstable angina;
* History of myocardial infarction within the past year;
* Supraventricular or ventricular arrhythmias requiring treatment or intervention
8. Pregnant or breastfeeding women (pregnancy testing should be considered for women of childbearing potential with active sexual life)
9. History or presence of other malignancies, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
10. Known hypersensitivity to macromolecule protein products or any component of benmelstobart.
11. Active infections requiring systemic treatment within 1 week prior to enrollment.
12. Administration of live vaccines within 30 days prior to the first dose of anlotinib hydrochloride.
13. History of organ transplantation or hematopoietic stem cell transplantation.
14. Presence of clinically significant bleeding symptoms or a definite hemorrhagic tendency; specifically, cases with a high risk of bleeding from local recurrence, or those within one year post-radiotherapy assessed to have a high risk of necrosis, must be excluded.
15. History of hypertension that remains poorly controlled with medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
16. Urinalysis showing urine protein ≥ ++, confirmed by 24-hour urine protein quantification ≥1.0 g.
17. Factors significantly affecting the absorption of oral drugs, such as inability to swallow, chronic diarrhea, or intestinal obstruction.
18. Any other condition assessed by the investigator as potentially compromising patient safety or compliance, such as severe illnesses requiring urgent treatment (including psychiatric disorders), significantly abnormal laboratory values, or other psychological, familial, or social risk factors.
