Overview
This phase III trial aims to evaluate the efficacy and safety of induction chemotherapy combined with serplulimab (induction/maintenance therapy) with omission of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).
Description
This multicenter phase III trial enrolls high-risk locally advanced nasopharyngeal carcinoma patients (AJCC 9th edition, Stage T1-3N2 \[II\] or T1-4N3/T4N1-2 \[III\]) who achieves ≥50% tumor regression (RECIST v1.1) and undetectable plasma EBV DNA after three cycles of GP induction chemotherapy (gemcitabine + cisplatin) combined with serplulimab. Eligible patients will be randomized to either:
Experimental arm: Radiotherapy alone followed by serplulimab maintenance, or Control arm: Cisplatin-based concurrent chemoradiotherapy (CCRT) followed by serplulimab maintenance.
Primary study endpoint
- event-free survival (EFS) ② overall survival (OS) ③ Incidence of Hearing Loss (any grade) Secondary study endpoints
- 3-year distant metastasis-free survival (DMFS)
- 3-year locoregional recurrence-free survival (LRFS)
- Quality of life (QoL) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 v3.0) and its head-and-neck cancer module (EORTC QLQ-H\&N35 v1.0), both validated Chinese versions.
- Incidence rate of investigator-reported adverse events (AEs)
- Incidence rate of patient-reported AEs
Eligibility
Inclusion Criteria:
- Age at diagnosis: 18-65 years;
- Pathologically confirmed treatment-naïve nasopharyngeal carcinoma of "non-keratinizing type (WHO classification)";
- Locoregionally advanced nasopharyngeal carcinoma staged per the 9th edition of the American Joint Committee on Cancer (AJCC) staging system: Stage II (T1-3N2), Stage III(T1-4N3 or T4N1-2);
- ECOG performance status: 0-1;
- Post-induction therapy requirements:
Radiological assessment showing ≥50% tumor regression (RECIST 1.1) Undetectable plasma EBV DNA levels;
- Adequate bone marrow function:
White blood cell count \>4×10⁹/L Hemoglobin \>90 g/L Platelet count \>100×10⁹/L;
- Normal hepatic/renal function:
Total bilirubin ≤1.5×upper limit of normal (ULN) AST/ALT ≤2.5×ULN Alkaline phosphatase ≤2.5×ULN Creatinine clearance ≥60 mL/min;
- Normal results for:
Thyroid function tests Amylase and lipase Pituitary function Inflammatory/infection markers Cardiac enzymes Electrocardiogram
Additional requirements:
Pulmonary function tests for smokers \>50 years Cardiac ultrasound + myocardial function tests for patients with ECG abnormalities or cardiovascular history (unless meeting exclusion criterion (8));
- Signed informed consent with willingness/compliance to follow study schedules for treatment, follow-up, and laboratory tests;
- For women of childbearing potential: Agreement to use reliable contraception (e.g., condoms, prescribed oral contraceptives) from screening until 1 year post-treatment.
Exclusion Criteria:
- Hepatitis B Virus (HBV) Infection:
HBsAg-positive with HBV DNA \>1×10³ copies/mL (patients with controlled viremia \[\<1×10³ copies/mL\] after antiviral therapy are eligible).
- Hepatitis C Virus (HCV) Infection: Anti-HCV antibody-positive.
- HIV/AIDS: Anti-HIV antibody-positive or diagnosed with acquired immunodeficiency syndrome (AIDS).
- Active Tuberculosis (TB): History of active TB within the past year (regardless of treatment status). Exception: Patients with adequately treated past TB (confirmed by standard anti-TB therapy) may be enrolled if \>1 year since completion of treatment.
- Active Autoimmune Diseases:Known or suspected autoimmune disorders (e.g., uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, or asthma requiring bronchodilators).
- Exceptions
Type 1 diabetes mellitus Hypothyroidism managed with hormone replacement Skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia). 6. Interstitial Lung Disease (ILD):
History of ILD or pneumonitis requiring oral/IV steroids within the past year. 7. Immunosuppressive Therapy:
Chronic systemic corticosteroids (≥10 mg prednisone equivalent/day) or other immunosuppressants within 4 weeks prior to enrollment. Inhaled/topical steroids are permitted. 8. Uncontrolled Cardiac Disease: Heart failure (NYHA class ≥2), Unstable angina, Myocardial infarction within the past year, Clinically significant arrhythmias requiring treatment. 9. Pregnancy/Lactation: Pregnant or breastfeeding women (urine/blood pregnancy test required for women of childbearing potential). 10. Concurrent Malignancies:
History of other malignancies except:
Adequately treated non-melanoma skin cancer, Carcinoma in situ of the cervix, Papillary thyroid carcinoma. 11. Hypersensitivity: Known allergy to any component of the study drugs or excipients. 12. Active Infections:
Systemic infections requiring treatment within 1 week prior to enrollment.
Live Vaccines:
13. Administration of live vaccines within 30 days before the first immunotherapy dose.
14. Organ Transplantation: History of allogeneic organ transplantation.
15. Other High-Risk Conditions:
Any condition that may compromise patient safety or compliance per investigator assessment (e.g., severe psychiatric disorders, life-threatening comorbidities, or social/familial risk factors).
