Short-course Tislelizumab Combined With Chemoradiotherapy for Nasopharyngeal Carcinoma

Short-course Tislelizumab Combined With Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled, Multicenter, Phase 3 Non-inferiority Clinical Trial

This trial aim to explore whether short-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 3 cycles of 400 mg q6w in the consolidation phase) yields non-inferior event-free survival compared to long-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 5 cycles of 400 mg q6w in the consolidation phase) in patients with locoregionally advanced nasopharyngeal carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Cancer; Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: tislelizumab; Drug: tislelizumab; Drug: Gemcitabine + cisplatin (GP); Drug: Cisplatin (100mg/m2); Radiation: intensity-modulated radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 418
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Ma; Phone Number: +862087343469; Email: majun2@mail.sysu.edu.cn
• Study Contact Backup: Name: Yelin Liang; Phone Number: +862087342370; Email: liangyl@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 and ≤65 years
2. Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
3. Eastern Cooperative Oncology Group performance score of 0-1.
4. Tumor staged as T4N1 and T1-4N2-3 disease (AJCC 9th edition).

5. Adequate marrow function:

   white blood cell count > 4 × 10⁹/L hemoglobin >90g/L and platelet count >100×10⁹/L

6. Adequate hepatic and renal function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN, Alkaline phosphatase ≤ 2.5 ×ULN, clearance rate ≥ 60 ml/min 7. Other laboratory and clinical criteria Normal: thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG); For patients aged >50 years with a history of smoking, normal pulmonary function test (PFT) results are required; For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any exclusion criteria listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits.

8. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.

9. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug.

Exclusion Criteria:

1. Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA >1×10 copies/mL, positive for anti-hepatitis C virus (HCV) antibody, positive for anti-hepatitis C virus (HCV) antibody
2. Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
3. Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received con dirmed and regular anti-tuberculosis treatment.
4. Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
5. History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
6. Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone >10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
7. Uncontrolled cardiac conditions, such as: Heart failure with New York Heart Association (NYHA) classi dication ≥ Class II; or Unstable angina; or History of myocardial infarction within the past year; or Supraventricular or ventricular arrhythmias requiring treatment or intervention
8. Pregnant or breastfeeding women (pregnancy testing should be considered for women of childbearing potential with active sexual life)
9. History or presence of other malignancies, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
10. Known hypersensitivity to macromolecule protein products.
11. Active infections requiring systemic treatment within 1 week prior to enrollment.
12. Administration of live vaccines within 30 days prior to the first dose of tile.
13. History of organ transplantation or hematopoietic stem cell transplantation.
14. Any other condition assessed by the investigator as potentially compromising patient safety or compliance, such as severe illnesses requiring urgent treatment (including psychiatric disorders), significantly abnormal laboratory values, or other psychological, familial, or social risk factors.
15. Patients who have previously received immune checkpoint (CTLA-4, PD-1, PD-L1, etc.) inhibitor therapy.

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
Experimental: tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant); Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.	Drug: tislelizumab; Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 3 cycles.; Drug: tislelizumab; Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 5 cycles.; Drug: Gemcitabine + cisplatin (GP); neoadjuvent gemcitabine (1000 mg/m2 d1, d8) and cisplatin (80 mg/m2 d1) every 3 weeks for 3 cycles; Drug: Cisplatin (100mg/m2); Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation; Radiation: intensity-modulated radiotherapy; Defnitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Active Comparator: tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant); Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.	Drug: tislelizumab; Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 3 cycles.; Drug: tislelizumab; Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 5 cycles.; Drug: Gemcitabine + cisplatin (GP); neoadjuvent gemcitabine (1000 mg/m2 d1, d8) and cisplatin (80 mg/m2 d1) every 3 weeks for 3 cycles; Drug: Cisplatin (100mg/m2); Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation; Radiation: intensity-modulated radiotherapy; Defnitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival (FFS)	From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	From date of randomization until the date of death from any cause, whichever came first	3 years
Distant metastasis-free survival (DMFS)	From date of randomization until the date of first documented distant metastasis, whichever occurred first	3 years
Locoregional recurrence-free survival (LRRFS)	From date of randomization until the date of first documented locoregional recurrence, whichever occurred first	3 years
Adverse events (AEs)	Graded according to CTCAE V5.0	within 5 years
Quality of life (QoL)	The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used.The change of QoL from randomization to 9 weeks (at the end of neoadjuvant treatment), 16 weeks (at the end of radiotherapy), 28 weeks (at the 3nd cycle of adjuvant tislelizumab treatment), 40 (at the 5nd cycle of adjuvant tislelizumab treatment, if available), 1 year, 2 years, 3 years, 4 years, and 5 years after randomization. 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.	week 0, 9, 16, 28, 40 and 1 year, 2 years, 3 years, 4 years, and 5 years after randomization
cost-effectiveness analysis	Cost-effectiveness will be evaluated as the incremental cost per clinical outcome achieved (e.g., cost per quality-adjusted life year gained or cost per event avoided) when comparing the intervention and control groups.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: tislelizumab; PD-1 antibody; short-course
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated; tislelizumab
• Other Study ID Numbers: 2025-FXY-462-FLK

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