Cadonilimab (PD-1/CTLA-4 Bispecific Blockade) and Chemoradiotherapy in Nasopharyngeal Carcinoma (GEMSTONE)

Inclusion Criteria:

1. Patients with histologically confirmed nasopharyngeal carcinoma.

2. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).

3. Eastern Cooperative Oncology Group performance status ≤1.

4. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L andplatelet count ≥100×10e9/L.

5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit ofnormal (ULN), and bilirubin ≤ 1.5×ULN.

6. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gaultformula).

7. Patients must be informed of the investigational nature of this study and givewritten informed consent.

8. Women of childbearing potential (WOCBP) who are sexually active must be willing toadhere to effective contraception during treatment and for 1 year after the lastdose of study drug. Men who are sexually active with WOCBP must be willing to adhereto effective contraception during treatment and for 1 year after the last dose ofthe study drug

Exclusion Criteria:

1. Age > 65 or < 18.

2. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3copies/ml or 200IU/ml

3. Hepatitis C virus (HCV) antibody positive

4. Has active autoimmune disease, except type I diabetes, hypothyroidism treated withreplacement therapy, and skin disease that doesn't require systemic treatment (e.g.,vitiligo, psoriasis, or alopecia).

5. Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent.Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhaleor topical corticosteroid will be allowed.

6. Has a known history of active TB (bacillus tuberculosis) within 1 year; patientswith adequately treated active TB over 1 year ago will be allowed.

7. Has a known history of interstitial lung disease.

8. Has received a live vaccine within 30 days before informed consent or will receive alive vaccine in the near future.

9. Is pregnant or breastfeeding.

10. Prior malignancy within 5 years, except in situ cancer, adequately treatednon-melanoma skin cancer, and papillary thyroid carcinoma.

11. Has known allergy to large molecule protein products or any compound of cadonilimab.

12. Has a known history of human immunodeficiency virus (HIV) infection.

13. Any other condition, including symptomatic heart failure, unstable angina,myocardial infarction, active infection requiring systemic therapy, mental illnessor domestic/social factors, deemed by the investigator to be likely to interferewith a patient's ability to sign informed consent, cooperate and participate in thestudy, or interferes with the interpretation of the results.