Tislelizumab Plus Chemotherapy With Response-Adapted Radiotherapy for de Novo Metastatic Nasopharyngeal Carcinoma: A Prospective, Phase II Trial

This study is aimed to evaluate the efficacy and safety of tislelizumab combined with chemotherapy and response-adapted radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Radiation: response-adapted radiotherapy

Detailed Description

This is a prospective phase II study that enrolled patients with previously untreated de novo metastatic nasopharyngeal carcinoma who achieved either a complete response (CR) or partial response (PR) after 4-6 cycles of treatment with gemcitabine plus cisplatin (GP regimen) chemotherapy combined with tislelizumab. Based on tumor response stratification, these patients received locoregional radiotherapy and radiotherapy for metastatic lesions, followed by sequential tislelizumab maintenance therapy.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400000
      • Chongqing University Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-70 years.
2. Newly diagnosed nasopharyngeal carcinoma with pathological confirmation of non-keratinizing carcinoma (WHO type II or III).
3. Stage IV (T1-4N0-3M1a and M1b) according to the AJCC/UICC 9th edition clinical staging system for NPC.
4. Achieved complete response (CR) or partial response (PR) by imaging evaluation after 4-6 cycles of GP chemotherapy combined with tislelizumab.
5. ECOG performance status: 0-1.
6. Adequate organ function.

Exclusion Criteria:

1. Recurrent or metastatic nasopharyngeal carcinoma after radical treatment.
2. Other malignancies diagnosed or treated within the past 5 years (except basal cell carcinoma, cervical carcinoma in situ, and superficial bladder tumors).
3. Previous treatment with immune checkpoint inhibitors.
4. Pregnancy or lactation (consider pregnancy testing for women of childbearing age and emphasize effective contraception during treatment).
5. Active or history of autoimmune diseases.
6. Concurrent medical condition requiring the use of immunosuppressive medications.
7. Active hepatitis B or C infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: response-adapted radiotherapy; This is a prospective phase II study that enrolled patients with previously untreated de novo metastatic nasopharyngeal carcinoma who achieved either a complete response (CR) or partial response (PR) after 4-6 cycles of treatment with gemcitabine plus cisplatin (GP regimen) chemotherapy combined with tislelizumab. Based on tumor response stratification, these patients received locoregional radiotherapy and radiotherapy for metastatic lesions, followed by sequential tislelizumab maintenance therapy.

Radiation: response-adapted radiotherapy; Induction Treatment Regimen: • Tislelizumab+Gemcitabine+Cisplatin for 4-6 cycles . Response-Adapted Radiotherapy: Patients achieving CR after induction therapy require no radiotherapy.; Patients achieving PR after induction therapy: Radiotherapy (55 Gy/20 fractions, 5 fractions per week, over 4 weeks) to the residual primary nasopharyngeal lesion and metastatic cervical lymph nodes. Radiotherapy for metastatic lesions concurrently or sequentially with locoregional radiotherapy. Immunotherapy Regimen: maintenance therapy with tislelizumab monotherapycontinues until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first. The total treatment duration shall not exceed 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	PFS is defined as the time from the initiation of treatment until the first occurrence of locoregional progression, distant metastatic progression, or death from any cause, whichever comes first.	1-year

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR	1-year
OS	1-year
Local Regional Control	1-year
Distant Metastasis Control	1-year
DoR	1-year

Collaborators and Investigators

• Sponsor: Chongqing University Cancer Hospital

Publications and helpful links

General Publications

• Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. 2. Ng SH, Chan SC, Yen TC, et al. Pretreatment evaluation of distant-site status in patients with nasopharyngeal carcinoma: accuracy of whole-body MRI at 3-Tesla and FDG-PET-CT. Eur Radiol. 2009;19(12):2965-2976. 3. Zou X, You R, Liu H, et al. Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer. 2017;77:117-126. 4. Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016;388(10054):1883-1892. 5. Yang Y, Pan J, Wang H, et al. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). Cancer Cell. 2023;41(6):1061-1072 e1064. 6. Mai HQ, Chen QY, Chen D, et al. Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial. JAMA. 2023;330(20):1961-1970. 7. Yang Y, Qu S, Li J, et al. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021;22(8):1162-1174. 8. You R, Liu YP, Huang PY, et al. Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1345-1352. 9. Chen SY, Duan XT, Li HF, et al. Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial. Cell Rep Med.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: tislelizumab; nasopharyngeal carcinoma; de novo metastatic
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma
• Other Study ID Numbers: Daybreak-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to ethical requirements, the data can be obtained via email.

Drug and device information, study documents

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