EBV Lytic Reactivation Therapy Combined With PD-1 Antibody in Recurrent/Metastatic Nasopharyngeal Carcinoma

August 16, 2025 updated by: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Efficacy and Safety of EBV Lytic Reactivation Therapy Combined With PD-1 Antibody in Recurrent/Metastatic Nasopharyngeal Carcinoma: a Single-center, Single-arm Phase II Trial

Nearly all undifferentiated nasopharyngeal carcinoma (NPC) are associated with the Epstein-Barr Virus (EBV), which typically remains in a latent, non-immunogenic state within tumor cells. By combining EBV lytic induction strategy with standard chemo-immunotherapy, this study aims to create a synergistic anti-tumor effect and improve clinical outcomes for patients with recurrent/metastatic NPC (r/m NPC). This is a phase II, single-center, single-arm clinical trial designed to evaluate the efficacy and safety of a novel combination therapy in patients with r/m EBV-positive NPC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Rationale: Epstein-Barr virus (EBV) is clonally present in nearly all undifferentiated nasopharyngeal carcinoma (NPC) tumor cells, particularly in endemic regions. In most cases, EBV remains in a latent state, expressing only a limited set of non-immunogenic proteins, which facilitates immune evasion by tumor cells. Chemotherapeutic agents such as gemcitabine and cisplatin can induce the EBV lytic cycle, activate valganciclovir hydrochloride, thereby enabling the selective killing of EBV-infected tumor cells. This strategy may act synergistically with immunotherapy. Early-phase clinical studies have demonstrated the safety and potential efficacy of this approach; however, larger-scale studies are required to confirm these findings.

Study Objectives: The primary objectives of this clinical trial are: 1.To assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS) in patients receiving chemotherapy combined with valganciclovir hydrochloride and PD-1 antibody. 2.To evaluate the safety profile, including acute and chronic toxicities.

Study Design and Treatment Regimen: Patients with histologically confirmed EBV-positive, recurrent or metastatic NPC will be enrolled. Patients will receive 4 to 6 cycles of gemcitabine, cisplatin, and PD-1 antibody, with oral administration of valganciclovir hydrochloride tablets during the first 3 cycles. Following completion of the 4 to 6 cycles, patients will continue PD-1 antibody maintenance therapy for up to two years or until disease progression, unacceptable toxicity, initiation of a new anticancer therapy, withdrawal of informed consent, or death.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen Universitty Cancer Center
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must voluntarily participate and provide written informed consent.
  • Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma (NPC) at enrollment, with positive EBERs by pathological immunohistochemistry.
  • Metastatic NPC includes both newly diagnosed metastatic disease and metastatic disease after failure of first-line therapy, as well as recurrent NPC not amenable to local regional treatment, with confirmed metastatic or recurrent disease and no prior treatment after diagnosis.
  • Age ≥ 18 years and ≤ 75 years, of any sex.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Expected survival time ≥ 3 months.
  • Baseline plasma EBV DNA > 0 copies/mL.
  • Adequate organ function confirmed by the following criteria (no blood component transfusions or use of hematopoietic growth factors within 2 weeks prior to study treatment initiation):
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; platelet count ≥ 100 × 10^9/L; hemoglobin ≥ 90 g/L. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (CrCl) ≥ 60 mL/min . Total bilirubin (TBil) ≤ 1.5 × ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (for patients with liver metastases, TBil ≤ 3 × ULN; AST and ALT ≤ 5 × ULN). Serum albumin ≥ 28 g/L.

Exclusion Criteria:

  • History of severe hypersensitivity reactions to other monoclonal antibodies or to any component of PD-1 inhibitors.
  • Receipt of radiotherapy, biological therapy (e.g., tumor vaccines, cytokines, or growth factors), or other immunotherapy (excluding PD-1 and PD-L1 inhibitors), or any other anti-tumor treatment within 28 days or 5 half-lives prior to the first dose of study drug, whichever is shorter.
  • Prior treatment targeting Epstein-Barr virus (EBV) specifically.
  • History of any Grade ≥3 bleeding event, as defined by CTCAE v5.0, within 4 weeks prior to screening, or patients deemed at high risk of bleeding by the investigator.
  • Presence of necrotic lesions within 4 weeks prior to screening, with high risk of major hemorrhage as judged by the investigator.
  • Known congenital or acquired immunodeficiency (e.g., HIV-positive individuals).
  • Requirement for systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to initiation of study treatment.
  • History of active tuberculosis (TB). Suspected active TB must be excluded through chest X-ray, sputum examination, and clinical assessment of signs and symptoms.
  • Patients with HBV DNA ≥1000 copies/mL. Patients with positive hepatitis C antibody results may only be enrolled if polymerase chain reaction (PCR) testing confirms HCV RNA negativity.
  • Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
  • History of other malignancies, except for adequately treated basal cell carcinoma or carcinoma in situ of the cervix.
  • Uncontrolled cardiovascular conditions, including but not limited to: Heart failure with NYHA classification ≥2; Unstable angina; Myocardial infarction within the past year; Supraventricular or ventricular arrhythmias requiring treatment or intervention.
  • Significant impairment of cardiac, hepatic, pulmonary, renal, or bone marrow function.
  • Severe and uncontrolled medical illnesses or infections.
  • Concurrent participation in another clinical trial or use of another investigational agent.
  • Refusal or inability to sign informed consent.
  • Any other contraindications to study treatment as determined by the investigator.
  • Individuals with personality disorders or psychiatric conditions, and those lacking or having limited legal capacity to provide consent.

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EBV Lytic Reactivation Therapy
Patients will receive 4 to 6 cycles of gemcitabine, cisplatin, and PD-1 antibody, with oral administration of valganciclovir hydrochloride tablets during the first 3 cycles. Following completion of 4 to 6 cycles, patients will continue with maintenance therapy using PD-1 antibody.
Drug: Valganciclovir Hydrochloride Tablets
Valganciclovir hydrochloride tablets will be administered at 900 mg twice daily from day 1 to day 14, followed by 450 mg twice daily from day 15 to day 20, for a total of 3 cycles.
Drug: gemcitabine, cisplatin, and PD-1 antibody

Gemcitabine 1000 mg/m² will be administered intravenously on days 1 and 8; cisplatin 80 mg/m² intravenously on day 1; and PD-1 antibody intravenously on day 1. Each cycle is 21 days in duration, and treatment will be administered for a total of 4 to 6 cycles.

Following completion of the 4 to 6 cycles, patients will continue PD-1 antibody maintenance therapy (every 3 weeks) for up to two years or until disease progression, unacceptable toxicity, initiation of a new anticancer therapy, withdrawal of informed consent, or death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate, ORR
Time Frame: From enrollment to the end of treatment. Up to 2 approximately years.
Objective Response Rate (ORR) is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 from the National Cancer Institute (NCI).
From enrollment to the end of treatment. Up to 2 approximately years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate，DCR
Time Frame: From enrollment to the end of treatment. Up to 2 approximately years.
Disease Control Rate (DCR) is defined as the proportion of patients who achieve tumor response classified as partial response (PR), complete response (CR), or stable disease (SD) according to recognized response evaluation criteria-such as RECIST version 1.1.
From enrollment to the end of treatment. Up to 2 approximately years.
Progression-free Survival, PFS
Time Frame: 1 years; 2 years; 5 years;
Defined as the time from registration to documented disease progression or non-cancer-specific death.
1 years; 2 years; 5 years;
Duration of Response, DoR
Time Frame: From enrollment to disease progression. Up to 2 approximately years.
Defined as the median length of time from the initial documentation of a tumor response (either complete response [CR] or partial response [PR]) to disease progression or death from any cause.
From enrollment to disease progression. Up to 2 approximately years.
Overall Survival, OS
Time Frame: 1 years; 2 years; 5 years
Defined as the time from registration to death from any cause.
1 years; 2 years; 5 years
Incidence rate of acute and late adverse events (AEs)
Time Frame: From enrollment to the end of follow-ups. Up to 2 approximately years.
Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs.
From enrollment to the end of follow-ups. Up to 2 approximately years.

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Hai-Qiang Mai, MD,PhD, Sun Yat-sen Universitty 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 (Estimated)

August 19, 2025

Primary Completion (Estimated)

August 18, 2026

Study Completion (Estimated)

August 18, 2031

Study Registration Dates

First Submitted

August 11, 2025

First Submitted That Met QC Criteria

August 16, 2025

First Posted (Actual)

August 24, 2025

Study Record Updates

Last Update Posted (Actual)

August 24, 2025

Last Update Submitted That Met QC Criteria

August 16, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-FXY-184

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Complete de-identified patient data set will be submitted to the Research Data Deposit (RDD) public platform (http://www.researchdata.org.cn) and available from the principal investigators upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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