Overview

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.

Eligibility

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.