Efficacy and Safety of TPC Induction Chemotherapy Combined With Nimotuzumab and Toripalimab "Immune Sandwich" Regimen Versus Full-Course Immunotherapy for Locally Advanced Nasopharyngeal Carcinoma

NCT07706985 | Recruiting Phase 3 DMC

• 1 other identifier: SYSKY-2026-425-02
• Study Type: interventional
• Target: 566
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma (NPC)

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomization to 3 years

Secondary Outcomes (5)

• Overall Survival

  From randomization to 3 years and 5 years

• Locoregional Recurrence-Free Survival

  From randomization to 3 years

• Distant Metastasis-Free Survival

  From randomization to 3 years

• Objective Response Rate

  9 weeks and 3 months

• Incidence of Treatment-Emergent Adverse Events

  Through treatment completion, an average of 1 year

Study Arms (2)

Full-Course Immunotherapy Group

ACTIVE COMPARATOR

Induction Chemotherapy Phase：TPC chemotherapy+ Toripalimab + Nimotuzumab； Concurrent Radiotherapy Phase：Nimotuzumab + Toripalimab； Adjuvant Treatment Phase：Toripalimab

Drug: Toripalimab combined with Nimotuzumab

Concurrent Immunotherapy-Omitted Group

EXPERIMENTAL

Induction Chemotherapy Phase：TPC chemotherapy+ Toripalimab + Nimotuzumab； Concurrent Radiotherapy Phase：Nimotuzumab； Adjuvant Treatment Phase：Toripalimab

Drug: Nimotuzumab

Interventions

Toripalimab combined with Nimotuzumab DRUG

Induction 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.

Full-Course Immunotherapy Group

Nimotuzumab DRUG

Induction 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.

Concurrent Immunotherapy-Omitted Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Adequate organ and bone marrow function as demonstrated by laboratory test results obtained within 7 days prior to enrollment. No blood products, hematopoietic growth factors, albumin, or other intravenous/subcutaneous corrective medications are permitted within 14 days before laboratory testing. Specific criteria are listed below.Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet (PLT) count ≥ 75 × 10⁹/L; Hemoglobin (HGB) ≥ 9.0 g/dL;Liver function: Total Bilirubin (TBIL) ≤ 2 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 5 × ULN; serum albumin ≥ 28 g/L; Alkaline Phosphatase (ALP) ≤ 5 × ULN. Renal function: Serum Creatinine (Cr) ≤ 1.5 × ULN, or Creatinine Clearance (CCr) ≥ 50 mL/min (calculated via the Cockcroft-Gault formula). For patients with urine protein ≥ 2+ on routine urinalysis, a 24-hour urine collection is required, with total 24-hour urinary protein quantification \< 1 g. Coagulation function: International Normalized Ratio (INR) ≤ 2.3, or prothrombin time (PT) prolongation ≤ 6 seconds
• Able to provide written informed consent and comply with all protocol-specified study visits and related procedures.

You may not qualify if:

• 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
• Active tuberculosis (TB) receiving anti-tuberculosis treatment, or having received anti-tuberculosis therapy within 1 year before the first study drug dose.
• Human immunodeficiency virus (HIV) infection (positive HIV 1/2 antibody), or known syphilis infection requiring treatment
• Severe active or poorly controlled infections. Severe infection requiring hospitalization within 4 weeks before the first dose, including but not limited to complications from infection, bacteremia, or severe pneumonia
• History of active autoimmune diseases requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, physiological corticosteroids for adrenal or pituitary insufficiency) are permitted. Known history of primary immunodeficiency. Subjects with only positive autoantibodies will be assessed by the investigator to confirm the presence of autoimmune disease
• Female patients who are pregnant or breastfeeding
• Prior radiotherapy, chemotherapy, or surgery for nasopharyngeal and cervical lesions (excluding biopsy)
• History of hypersensitivity to any study drug or its components

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

nimotuzumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Liu Guoying

CONTACT

18127919832; liugy0109@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 16, 2026
• Study Start: July 20, 2026
• Primary Completion (Estimated): July 20, 2030
• Study Completion (Estimated): July 20, 2033
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)