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

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.

Study Overview

• Status: Recruiting
• Conditions: Distant Metastasis; Nasopharangeal Cancer
• Intervention / Treatment: Radiation: Immediate locoregional radiotherapy; Radiation: Salvage locoregional radiotherapy

Detailed Description

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China, with approximately 15% of patients presenting with distant metastases at diagnosis. A PD-1 inhibitor combined with gemcitabine and cisplatin (GP) has become the standard first-line therapy for metastatic NPC. However, the survival benefit of adding immediate locoregional radiotherapy to PD-1 inhibitor plus GP in de novo metastatic NPC remains uncertain. This phase III randomized trial is designed to compare immediate versus salvage locoregional radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with the objective of determining whether salvage radiotherapy is non-inferior to immediate radiotherapy while offering reduced toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Haiqiang Mai, PhD, MD; Phone Number: +86-020-87343643; Email: maihq@sysucc.org.cn

Study Locations

• China
  • Changsha, China
    • Not yet recruiting
    • Hunan Cancer Hospital
    • Contact: Feng Liu, MD, PhD; Phone Number: 008618613985727; Email: liufeng@hnca.org.cn
  • Fuzhou, China
    • Not yet recruiting
    • Fujian Cancer Hospital
    • Contact: Sufang Qiu, MD, PhD; Phone Number: 0086059183660063; Email: sufangqiu@fjmu.edu.cn
  • Hangzhou, China
    • Not yet recruiting
    • Zhejiang Cancer Hospital
    • Contact: Xiaozhong Chen, MD, PhD; Phone Number: 0086057188122186; Email: chenxiaozhong2016@163.com
  • Nanning, China
    • Not yet recruiting
    • Guangxi Medical University Cancer Hospital
    • Contact: Song Qu, MD, PhD; Phone Number: 008607715331422; Email: qusong@sr.gxmu.edu.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Haiqiang Mai, PhD, MD; Phone Number: 00862087343643; Email: maihq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-70 years, any gender.
2. 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.
3. ECOG performance status 0-1.
4. Stage IV NPC according to the 9th edition of the UICC/AJCC staging system.
5. No prior anti-tumor treatment for NPC (radiotherapy, chemotherapy, surgery, etc.).
6. Expected survival ≥ 3 months.
7. At least one measurable lesion per RECIST v1.1.
8. Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.

9. 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

10. 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 Criteria:

1. Prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
2. Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
3. Presence of uncontrolled or symptomatic central nervous system (CNS) metastases.
4. History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer.
5. 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.
6. 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.
7. Hepatitis B: HBsAg positive with peripheral blood HBV DNA ≥ 1000 copies/mL
8. Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative
9. HIV infection
10. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia).
11. Interstitial lung disease, non-infectious pneumonitis, or history of ≥ grade 2 pneumonitis.
12. Major surgery within 4 weeks before enrollment, or unhealed surgical wound.
13. Pregnant or breastfeeding women, or those planning pregnancy during the study period.
14. Known allergy or hypersensitivity to study drugs or their excipients.
15. Any condition that, in the investigator's judgment, would interfere with trial participation or interpretation of results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate locoregional radiotherapy group; Immediate locoregional radiotherapy	Radiation: Immediate locoregional radiotherapy; 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.
Experimental: Salvage locoregional radiotherapy group; Salvage locoregional radiotherapy	Radiation: Salvage locoregional radiotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from random assignment to death from any cause.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional progression-free survival	Defined as the time from random assignment to the occurrence of a locoregional progression.	2 year
Distant progression-free survival	Defined as the time from random assignment to the occurrence of a distant progression.	2 year
Progression free-survival	Defined as the time from random assignment to locoregional or distant progression, or death from any cause.	2 year
Incidence of Acute and Late Toxicity	Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.	2 year
Quality of life (QoL)	The change of QoL from randomization to 1month, 3 months, 6 months and 1 year randomization. Assessed using the EORTC QoL questionnaire-C30 (EORTC QLQ-C30) version 3.0. This questionnaire comprises 30 questions, 24 aggregated into nine multi-question scales: five functioning scales (e.g., physical), three symptom scales (e.g., fatigue), and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual of EORTC QLQ-C30.	1 year
Quality of life (QoL)	The change of QoL from randomization to 1month, 3 months, 6 months and 1 year randomization.QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): November 20, 2025
• Primary Completion (Estimated): November 20, 2031
• Study Completion (Estimated): November 20, 2034

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Locoregional radiotherapy
• Other Study ID Numbers: 2025-FXY-252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No