Toripalimab Combined With Different Platinum-Based Induction Chemotherapy Regimens for Locally Advanced Nasopharyngeal Carcinoma

This phase II randomized trial compares the efficacy and safety of Toripalimab combined with three different platinum-based induction chemotherapy regimens, sequentially followed by standard concurrent chemoradiotherapy, for the treatment of locally advanced nasopharyngeal carcinoma (NPC). The enrolled patients will be 1:1:1 randomly assigned to receive induction chemotherapy of Gemcitabine plus Cisplatin plus Toripalimab(GP plus Toripalimab regimen), Nab-paclitaxel plus Cisplatin plus Toripalimab (TP plus Toripalimab regimen) or Nab-paclitaxel plus Cisplatin plus Capecitabine plus Toripalimab(TPC plus Toripalimab regimen).The study is aimed to pick up the most effective platinum-based induction chemotherapy regimen plus Toripalimab for these patients which provides the most survival benefit.

Inclusion criteria

• Age between 18 and 70 years, male or non-pregnant female.
• Pathologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Stage Any T, N2-3 or T4, N1 (AJCC 9th edition staging), with no distant metastasis (M0).
• ECOG performance status score of 0 or 1.
• Adequate hematological function: Hemoglobin (HGB)≥90g/L, Absolute Neutrophil Count (ANC) ≥ 1.5*10^9/L, and Platele (PLT) ≥100*10^9/L.
• Adequate hepatic function: ALT and AST≤2.5*Upper Limit of Normal (ULN), total bilirubin ≤2.0*ULN, and serum albumin≥30g/L.
• Adequate renal function: Serum creatinine ≤ 1.5*ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).
• International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 *ULN (unless the subject is receiving anticoagulant therapy and the coagulation parameters (PT/INR and APTT) are within the expected therapeutic range for the anticoagulant at the time of screening).

Exclusion criteria

• Patients with nasopharyngeal carcinoma presenting with recurrence or distant metastasis.
• Pathologically confirmed diagnosis of keratinizing squamous cell carcinoma (WHO Type I).
• Prior history of radiotherapy or systemic chemotherapy.
• Women who are pregnant, lactating, or of childbearing potential not employing effective contraception.
• HIV-positive status.
• History of other malignancies (except for cured basal cell carcinoma or carcinoma in situ of the cervix).
• Patients previously treated with immune checkpoint inhibitors (e.g., CTLA-4, PD-1, PD-L1 inhibitors).
• Patients with immunodeficiency diseases or a history of organ transplantation.
• Patients who have received high-dose glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressive therapy within 4 weeks prior.
• Patients with significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function.
• Concurrent use of other investigational drugs or current participation in another clinical trial.
• Patients who refuse or are unable to provide signed informed consent for trial participation.
• Patients with personality or psychiatric disorders, or those lacking legal capacity or with limited legal capacity.
• Hepatitis B surface antigen (HBsAg) positive with peripheral blood Hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000 copies/ml.
• Patients with positive Hepatitis C virus (HCV) antibody test results are eligible only if the HCV ribonucleic acid (RNA) polymerase chain reaction test result is negative.
• Arterial or venous thrombotic events within 6 months prior to screening initiation, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Known history of active tuberculosis (TB). Subjects suspected of having active TB must be evaluated and ruled out via chest X-ray, sputum examination, and clinical signs and symptoms.

21.Any other severe, uncontrolled medical condition, infection, or treatment contraindication, or any other condition that, in the investigator's judgment, may pose a risk for receiving the investigational drug, or may interfere with the assessment of the investigational drug, subject safety, or interpretation of the study results.