PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Salvage Locoregional Radiotherapy in De Novo Metastatic NPC

NCT07235319 | Recruiting Phase 3 DMC

• 1 other identifier: 2025-FXY-252
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Nasopharangeal Cancer; Distant Metastasis

Keywords

Locoregional radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Defined as the time from random assignment to death from any cause.

  2 year

Secondary Outcomes (6)

• Locoregional progression-free survival

  2 year

• Distant progression-free survival

  2 year

• Progression free-survival

  2 year

• Incidence of Acute and Late Toxicity

  2 year

• Quality of life (QoL)

  1 year

Study Arms (2)

Immediate locoregional radiotherapy group

ACTIVE COMPARATOR

Immediate locoregional radiotherapy

Radiation: Immediate locoregional radiotherapy

Salvage locoregional radiotherapy group

EXPERIMENTAL

Salvage locoregional radiotherapy

Radiation: Salvage locoregional radiotherapy

Interventions

Immediate locoregional radiotherapy RADIATION

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.

Immediate locoregional radiotherapy group

Salvage locoregional radiotherapy RADIATION

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.

Salvage locoregional radiotherapy 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:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (5)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Hunan Cancer Hospital

Changsha, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, China

NOT YET RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, China

NOT YET RECRUITING

Central Study Contacts

Haiqiang Mai, PhD, MD

CONTACT

+86-020-87343643; maihq@sysucc.org.cn

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: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 19, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): November 20, 2031
• Study Completion (Estimated): November 20, 2034
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)