This is an Open Label, Non-Inferiority, Multicenter, Randomized Phase 3 Trial aimed to investigate the impact of reduced-dose radiotherapy in combination with chemotherapy and immunotherapy on patients' prognosis and complication compared with conventional-dose radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive stage III NPC patients screened out according to the treatment response.

The goals of this clinical trial includes: ① To confirm whether LRRFS after reduced-dose radiotherapy in combination with chemotherapy and immunotherapy is non-inferior to LRRFS after conventional-dose radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive stage III NPC patients screened out according to the treatment response; ② To explore the impact of reduced-dose radiotherapy on 3-year OS, 3-year PFS, 3-year DMFS, 3-year LRFS and 3-year RRFS for treatment-sensitive stage III NPC patients screened out according to the treatment response; ③ To explore the impact of reduced-dose radiotherapy on radiotherapy complications and quality of life; ④ To explore the interaction between different clinical factors and the impact of reduced-dose radiotherapy on the prognosis of patients; ⑤ To explore the biomarkers of sensitivity to chemotherapy and radiotherapy for patients with nasopharyngeal carcinoma and the underlying mechanism.

For these purposes, we plan to prospectively enroll stage III NPC patients from hospitals in China. The participants will receive 3 cycles of induction chemotherapy (GP regimen + Camrelizumab) followed by intensity-modulated radiation therapy. 2 cycles of concurrent chemotherapy will be administered during the radiotherapy. Patients' treatment response will be evaluated with MRI examination after 27 fractions of radiotherapy. If the treatment response after 27 fractions of radiotherapy is complete remission, the participants will be randomized into reduced-dose radiotherapy group and conventional-dose radiotherapy group. If the treatment response after 27 fractions of radiotherapy is not complete remission, the participants will be assigned to the unenrolled group. All the participants in the unenrolled group will receive conventional-dose radiotherapy. After the radiotherapy, all the participants will receive 9 cycles of Camrelizumab immunotherapy. Besides, all the participants in the unenrolled group will also receive metronomic adjuvant capecitabine chemotherapy for 1 year. The prognosis, complication, and quality of life will be compared between the reduced-dose radiotherapy group and the conventional-dose radiotherapy group.

Inclusion Criteria:

1. Age: 18 Years to 65 Years;
2. Eastern Cooperative Oncology Group performance status ≤1;
3. Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma, the pathological type is non-keratinising carcinoma;
4. Tumor staged as Stage III (T3N0 Excepted; AJCC 8th);
5. Patients' lymph node without adverse features (no central necrosis, no muscle/skin invasion, no lymph node fusion);
6. Normal bone marrow function: white blood cell count > 4×10^9/L, hemoglobin > 90g/L, platelet count > 100×10^9/L;
7. Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine transaminase and aspartate transaminase ≤ 2.5 × ULN, alkaline phosphatase ≤ 2.5 × ULN, creatinine clearance rate ≥ 60 ml/min;
8. Receive 3 cycles of indction chemotherapy (GP regimen + Camrelizumab);
9. Plasma EBV DNA after the second cycle of concurrent chemotherapy: negative;
10. Complete remission after 27 fractions of radiotherapy based on the MRI examination of the nasopharynx and neck (According to Response Evaluation Criteria in Solid Tumors 1.1);
11. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
12. Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.

Exclusion Criteria:

1. Hepatitis B virus surface antigen (HBsAg) positive and Hepatitis B virus DNA > 1000 copies/ml;
2. Anti-hepatitis C virus positive;
3. Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
4. Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment, history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
5. Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
6. Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
7. Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
8. Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2), 2) unstable angina, 3) myocardial infarction in past 1 year, 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
9. Active infection requiring systemic treatment;
10. Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
11. History of radiotherapy, except for non-melanoma skin cancer located outside the target volume of radiotherapy for nasophayngeal carcinoma;
12. Receive treatment for the local or regional disease other than that specified in the research plan;
13. Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
14. Allergy to macromolecular protein preparations, or any component of Camrelizumab;
15. Receiving live vaccine within 30 days of the initial Camrelizumab;
16. Contraindications to MRI examination, for example: claustrophobia, allergy to MRI contrast;
17. History of psychotropic disease, alcoholism or drug abuse, and other situation assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.

Complete de-identified patient data set will be submitted onto the Research Data Deposit (RDD) public platform (http://www.researchdata.org.cn) and available from the principal investigators upon reasonable request.