In order to explore the efficacy and safety of targeted therapy and immunotherapy combined with GP chemotherapy in the treatment of high risk advanced nasopharyngeal carcinoma, the investigators design a single-arm, Phase II clinical trial targeted high-risk patients with local stage nasopharyngeal carcinoma (stage IVa: TanyN3M0/T4N0-2M0,8th AJCC/UICC staging) for Toripalimab Plus Anlotinib Combined With GP Induction Chemotherapy and Concurrent Chemoradiotherapy Followed by Toripalimab Maintenance Therapy.

In order to explore the efficacy and safety of targeted therapy and immunotherapy combined with GP chemotherapy in the treatment of high risk advanced nasopharyngeal carcinoma, the investigators design a single-arm, Phase II clinical trial targeted high-risk patients with local stage nasopharyngeal carcinoma (stage IVa: TanyN3M0/T4N0-2M0,8th AJCC/UICC staging) for Toripalimab Plus Anlotinib Combined With GP Induction Chemotherapy and Concurrent Chemoradiotherapy Followed by Toripalimab Maintenance Therapy. The investigators focus on the 2-year PFS as the primary outcome.

Inclusion Criteria:

• Voluntarily participate in and sign informed consent in person.
• Age 18-65, male or non-pregnant female.
• Pathological diagnosis of nasopharyngeal non-keratonic carcinoma (differentiated or undifferentiated, i.e., WHO type II or III).
• First treatment patients who did not receive antitumor therapy had no history of other malignant tumors;
• Stage IVa: TanyN3M0/T4N0-2M0 (8th AJCC/UICC stage)
• ECOG score 0-1, no serious dysfunction of heart, lung, liver, kidney and other vital organs.
• Hemoglobin (HGB) ≥90 g/L, white blood cells (WBC) ≥4.0×109 /L, platelets (PLT) ≥100×109 /L.
• Liver function: ALT and AST< 2.5 times the upper limit of normal (ULN), total bilirubin <2.0×ULN.
• Renal function: serum creatinine <1.5×ULN.

Exclusion Criteria:

• Patients with recurrent and distant metastasis of nasopharyngeal carcinoma.
• The pathology was keratinized squamous cell carcinoma (WHO type I).
• Received systemic or local glucocorticoid therapy within 4 weeks prior to enrollment.
• Participants who had participated in other drug clinical trials within 3 months before treatment.
• Patients with a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Patients with idiopathic pulmonary fibrosis, drug-induced pneumonia, institutional pneumonia (i.e., bronchiolitis obliterans), radiation pneumonia with clinical symptoms or requiring steroid treatment, active pneumonia, or other moderate to severe lung diseases that seriously affect lung function
• Have a comorbiditis that requires long-term treatment with immunosuppressive drugs or systemic or local use of immunosuppressive doses of corticosteroids.
• Prior use of anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies (or any other antibody that acts on the T-cell co-stimulation or checkpoint pathway), and efficacy was assessed as progressive at enrollment.
• The subject has any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; Patients with vitiligo or who had complete remission of asthma in childhood and did not require any intervention as adults were included; Patients with asthma requiring medical intervention with bronchodilators were not included).
• Positive HBV DNA copy number was detected in HIV-positive patients and HBsAg positive patients (quantitative detection ≥ 1000cps/ml); Chronic hepatitis C blood screening positive (HCV antibody positive) with HCV RNA positive detection.
• Received any anti-infection vaccine (such as influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment.
• Pregnancy test positive women of childbearing age and breastfeeding women.
• Patients who are unable to cooperate with regular follow-up due to psychological, social, family and geographical reasons.

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