Immunotherapy combined with chemoradiotherapy has become standard care for locally advanced nasopharyngeal carcinoma, yet radiotherapy-induced lymphopenia may impair the efficacy of concurrent PD-1 blockade. Existing evidence supports synergistic anti-tumor activity between the anti-EGFR antibody nimotuzumab and toripalimab. This multicenter, open-label, non-inferiority Phase III trial randomizes eligible stage III-IVA LA-NPC patients 1:1 to two arms. The experimental group receives an "immune sandwich" regimen: TPC induction plus nimotuzumab and toripalimab, concurrent radiotherapy with weekly nimotuzumab only, followed by toripalimab maintenance. The control arm adopts full-course toripalimab throughout induction, concurrent radiotherapy and adjuvant phases. The primary endpoint is 3-year event-free survival, with secondary endpoints covering overall survival, local/distant control rates, objective response rate and treatment-related toxicities. A total of 566 subjects will be enrolled to verify whether the simplified sandwich strategy delivers non-inferior survival with better safety profiles.
Aged between 18 and 70 years, regardless of gender
Histologically or cytologically confirmed diagnosis of nasopharyngeal carcinoma
Locoregionally advanced nasopharyngeal carcinoma classified as Stage III-IVA per the 8th AJCC staging system, excluding T3-4N0 and T3N1 disease
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Diagnosis of another malignant tumor within 5 years prior to the first study drug administration, excluding radically treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ
Symptomatic congestive heart failure (New York Heart Association [NYHA] Class II-IV) or left ventricular ejection fraction (LVEF) <50% on echocardiography
Patients with acute or chronically active hepatitis B or hepatitis C infection: HBV DNA >2000 IU/mL or 10⁴ copies/mL; HCV RNA >10³ copies/mL; concurrent positive hepatitis B surface antigen (HBsAg) and anti-HCV antibody. Subjects with viral loads below the above thresholds after nucleotide antiviral therapy are eligible for enrollment
Past or current history of pulmonary diseases including pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-induced pneumonitis, or severely impaired pulmonary function
Parallel
Toripalimab combined with Nimotuzumab
DrugInduction Chemotherapy Phase： TPC chemotherapy regimen: Nab-paclitaxel: 200 mg/m², intravenous infusion on Day 1；Cisplatin: 60 mg/m², intravenous infusion on Day 1；Capecitabine: 1000 mg/m² orally twice daily on Days 1-14；Each cycle lasts 21 days, for a total of 3 cycles. Toripalimab: 240 mg toripalimab injection, intravenous infusion on Day 0; 21-day cycles for 3 cycles total. Nimotuzumab: 400 mg nimotuzumab, intravenous infusion on Days 0 and 8; 21-day cycles for 3 cycles total. Concurrent Radiotherapy Phase： Toripalimab: 240 mg toripalimab injection via intravenous infusion starting on the first day of radiotherapy, administered every 21 days for 3 cycles. Nimotuzumab: 200 mg nimotuzumab via intravenous infusion once weekly for 6 consecutive weeks, starting on the first day of radiotherapy. Adjuvant Phase： Toripalimab injection 240 mg is administered via intravenous infusion once every 21 days per cycle.
Nimotuzumab
DrugInduction Chemotherapy Phase： TPC chemotherapy regimen: Nab-paclitaxel: 200 mg/m², intravenous infusion on Day 1；Cisplatin: 60 mg/m², intravenous infusion on Day 1；Capecitabine: 1000 mg/m² orally twice daily on Days 1-14；Each cycle lasts 21 days, for a total of 3 cycles. Toripalimab: 240 mg toripalimab injection, intravenous infusion on Day 0; 21-day cycles for 3 cycles total. Nimotuzumab: 400 mg nimotuzumab, intravenous infusion on Days 0 and 8; 21-day cycles for 3 cycles total. Concurrent Radiotherapy Phase： Nimotuzumab: 200 mg nimotuzumab via intravenous infusion once weekly for 6 consecutive weeks, starting on the first day of radiotherapy. Adjuvant Phase： Toripalimab injection 240 mg is administered via intravenous infusion once every 21 days per cycle.
Event-Free Survival
Defined as the time from the date of randomization to the first documented tumor progression (assessed per RECIST Version 1.1, regardless of continued study treatment) or death from any cause, whichever occurs first.
Overall Survival
Defined as the time from randomization to death from any cause.
Locoregional Recurrence-Free Survival
Defined as the time from randomization to the first documented locoregional tumor recurrence.
Distant Metastasis-Free Survival
Defined as the time from randomization to the first documentation of distant tumor metastasis.
Objective Response Rate
The proportion of subjects achieving complete response (CR) or partial response (PR) assessed per RECIST Version 1.1 at the completion of radiotherapy in the analysis population.
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Sun Yat-sen University
Lead sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Collaborator
