Neoadjuvant and Adjuvant Tislelizumab for Nasopharyngeal Carcinoma

May 27, 2026 updated by: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

A Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Tislelizumab + Chemotherapy Followed by Adjuvant Tislelizumab for the Treatment of Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and tislelizumab in neoadjuvant therapy combined with tislelizumab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma(NPC). Gemcitabine plus cisplatin(GP) has been demonstrated an effective chemotherapy regimen for NPC patients in previous studies. The results of GP combined with concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma showed 10% of locoregionally advanced NPC patients had complete response after three cycles of GP neoadjuvant chemotherapy, and GP neoadjuvant chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as compared with chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based neoadjuvant chemotherapy in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Recently, immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1)monoclonal antibody has shown promising efficacy in the treatment of tumor patients. Clinical trials have shown objective response rates of 20.5%-34% in patients with recurrent or metastatic NPC patients receiving anti PD-1 monoclonal antibody immunotherapy including pembrolizumab, nivolumab, camrelizumab, and toripalimab. The current NCCN guidelines recommend anti PD-1 monoclonal antibody as a second-line treatment for recurrent or metastatic NPC. More and more evidence show that immunotherapy combined with chemotherapy has a synergistic effect in treating tumors. GP chemotherapy combined with anti PD-1 antibody has achieved the initial effect in NPC. Phase 1 trials have shown the combination of camrelizumab plus GP chemotherapy in recurrent or metastatic NPC led to a proportion of 91% patients achieving an objective response. In addition, previous studeis showed that PD-1 antibody adjuvant therapy had good feasibility and effectiveness in the treatment of nasopharyngeal carcinoma. Tislelizumab, approved by the National Medical Products Administration in China, is an anti-PD-1 monoclonal IgG4 antibody with higher affinity to PD-1 than pembrolizumab and nivolumab and was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Multiple clinical trials have shown strong anti-neoplastic activity of tislelizumab in various tumors including NPC. Clinical trial has shown an objective response rates of 43% in patients with recurrent metastatic nasopharyngeal carcinoma treated with tirelizumab, which is superior to other anti PD-1 monoclonal antibodys. So we hypothesize that GP neoadjuvant chemotherapy combined with tislelizumab and tislelizumab adjuvant therapy could further improve survival of patients with locaregionally advanced NPC. Based on this, this study aims to evaluate the efficacy and safety of gemcitabine plus cisplatin chemotherapy combined with tislelizumab neoadjuvant therapy, followed by cisplatin based concurrent chemoradiotherapy, then followed by tislelizumab adjuvant therapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for individualized comprehensive treatment in NPC.

Study Type

Interventional

Enrollment (Actual)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Zhanjiang, Guangdong, China
        • The Affiliated Hospital of Guangdong Medical College
    • Guangxi
      • Wuzhou, Guangxi, China
        • Wuzhou Red Cross Hospital
    • Guizhou
      • Guiyang, Guizhou, China
        • Guizhou Cancer Hospital
    • Hunan
      • Changsha, Hunan, China
        • Hunan Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients must be informed of the investigational nature of this study and give written informed consent.
  2. Age ≥ 18 years and ≤70 years,men or non-pregnant women.
  3. Patients with histologically confirmed Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
  4. Tumor staged as III-IVA (AJCC 8th, except T3N0，T3N1(Only retropharyngeal lymph nodes metastasized).
  5. No previous anti-tumor treatment.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  7. Adequate marrow function:White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
  8. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.

Exclusion Criteria:

  1. Patients with recurrent or metastatic nasopharyngeal carcinoma.
  2. Histologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
  3. Prior therapy with radiation or systemic chemotherapy.
  4. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
  5. Seropositivity for human immunodeficiency virus (HIV).
  6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
  7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
  8. Patients with immunodeficiency disease or a history of organ transplantation.
  9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
  10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
  11. Patients with severe, uncontrolled disease or infections.
  12. Received other research drugs or in other clinical trials at the same time.
  13. Refuse or fail to sign the informed consent .
  14. Patients with other treatment contraindications.
  15. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.
  16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml.
  17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.
  18. Patients who were known to be intolerable or allergic to treatment drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GP combined with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy
Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and tislelizumab(200mg) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) ,then followed by adjuvant therapy with tislelizumab(200mg) every three weeks for eight cycles after radiotherapy
Drug: Tislelizumab
GP combine with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy
Other Names:
  • BGB-A317
Placebo Comparator: GP combine with Placebo neoadjuvant therapy+CCRT+Placebo adjuvant therapy
Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and Placebo(200mg) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) ,then followed by adjuvant therapy with Placebo(200mg) every three weeks for eight cycles after radiotherapy
Drug: Placebo
GP combine with Placebo neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 3 years
defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
3 years
Complete Response
Time Frame: 9 weeks
CR assessed by masked Central Imaging Review Committee (CIRC), according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the neoadjuvant therapy. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) .
9 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival(OS)
Time Frame: 3 years
defined as the time from random assignment to death from any cause or censored at the date of last follow-up.
3 years
Locoregional failure-free survival(LRRFS)
Time Frame: 3 years
defined as the time from random assignment to local or regional relapse, or death from any cause.
3 years
Distant metastasis-free survival(DMFS)
Time Frame: 3 years
defined as the time from random assignment to distant metastasis, or death from any cause.
3 years
Number of participants with adverse events
Time Frame: up to 3 years
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related acute adverse events were assessed by CTCAE v5.0 and late adverse events were assesed by the Late Radiation Morbidity Scoring Scheme of the Radiation Therapy Oncology Group.
up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Wuzhou Red Cross Hospital
Hunan Cancer Hospital
Cancer Hospital of Guizhou Province
Affiliated Hospital of Guangdong Medical University

Investigators

  • Principal Investigator: haiqiang Mai, MD, Sun Yat-sen University Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 10, 2022

Primary Completion (Estimated)

June 2, 2026

Study Completion (Estimated)

June 2, 2028

Study Registration Dates

First Submitted

January 11, 2022

First Submitted That Met QC Criteria

January 13, 2022

First Posted (Actual)

January 27, 2022

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-FXY-452

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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