PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Salvage Locoregional Radiotherapy in De Novo Metastatic NPC
A Multicenter, Open-Label, Randomized Phase III Non-Inferiority Trial of PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Salvage Locoregional Radiotherapy in De Novo Metastatic Nasopharyngeal Carcinoma
Sun Yat-sen University
260 participants
Nov 20, 2025
INTERVENTIONAL
Conditions
Summary
This phase III randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus salvage locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma. The study aims to evaluate whether salvage locoregional radiotherapy is non-inferior to immediate radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with potential for reduced toxicity.
Eligibility
Inclusion Criteria11
- Age 18-70 years, any gender.
- Histologically confirmed differentiated non-keratinizing carcinoma or undifferentiated non-keratinizing carcinoma by tissue biopsy, with radiologically detectable metastatic lesions. Pathological confirmation of metastatic lesions is recommended but not mandatory.
- ECOG performance status 0-1.
- Stage IV NPC according to the 9th edition of the UICC/AJCC staging system.
- No prior anti-tumor treatment for NPC (radiotherapy, chemotherapy, surgery, etc.).
- Expected survival ≥ 3 months.
- At least one measurable lesion per RECIST v1.1.
- Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
- Adequate organ function within 14 days before first dose, defined as:
- Hematology：Hemoglobin ≥ 90 g/L，ANC ≥ 1.5 × 10⁹/L，Platelet count ≥ 100 × 10⁹/L Renal Function：Creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) / eGFR ≥ 60 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN in the presence of liver metastases
- INR or PT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range，aPTT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range
Exclusion Criteria15
- Prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
- Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
- Presence of uncontrolled or symptomatic central nervous system (CNS) metastases.
- History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer.
- Active autoimmune disease or history of autoimmune disease requiring systemic treatment (e.g., corticosteroids, immunosuppressants) within the past 2 years, except for stable hypothyroidism, type 1 diabetes mellitus, or resolved childhood asthma/atopy.
- Known history of active pulmonary tuberculosis (TB). Suspected active TB must be excluded by chest X-ray, sputum examination, and assessment of clinical signs and symptoms.
- Hepatitis B: HBsAg positive with peripheral blood HBV DNA ≥ 1000 copies/mL
- Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative
- HIV infection
- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia).
- Interstitial lung disease, non-infectious pneumonitis, or history of ≥ grade 2 pneumonitis.
- Major surgery within 4 weeks before enrollment, or unhealed surgical wound.
- Pregnant or breastfeeding women, or those planning pregnancy during the study period.
- Known allergy or hypersensitivity to study drugs or their excipients.
- Any condition that, in the investigator's judgment, would interfere with trial participation or interpretation of results.
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Interventions
Immediate locoregional radiotherapy (LRRT) with concurrent chemotherapy + PD-1 inhibitor Maintenance. Concurrent chemotherapy: Cisplatin (DDP) 80mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.
PD-1 inhibitor maintenance + Salvage locoregional radiotherapy PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck while metastatic lesions remain controlled, salvage locoregional radiotherapy\* will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years. \*Concurrent chemotherapy: Cisplatin (DDP) 80 mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.
Locations(5)
View Full Details on ClinicalTrials.gov
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NCT07235319