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

NCT07138989 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-FXY-184
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Cancinoma (NPC)

Keywords

nasopharyngeal carcinoma; Epstein-Barr virus; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate, ORR

  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 Outcomes (5)

• Disease Control Rate，DCR

  From enrollment to the end of treatment. Up to 2 approximately years.

• Progression-free Survival, PFS

  1 years; 2 years; 5 years;

• Duration of Response, DoR

  From enrollment to disease progression. Up to 2 approximately years.

• Overall Survival, OS

  1 years; 2 years; 5 years

• Incidence rate of acute and late adverse events (AEs)

  From enrollment to the end of follow-ups. Up to 2 approximately years.

Study Arms (1)

EBV Lytic Reactivation Therapy

EXPERIMENTAL

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; Drug: gemcitabine, cisplatin, and PD-1 antibody

Interventions

Valganciclovir Hydrochloride Tablets DRUG

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.

EBV Lytic Reactivation Therapy

gemcitabine, cisplatin, and PD-1 antibody DRUG

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.

EBV Lytic Reactivation Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen Universitty Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (4)

• Ghosh SK, Perrine SP, Williams RM, Faller DV. Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents. Blood. 2012 Jan 26;119(4):1008-17. doi: 10.1182/blood-2011-06-362434. Epub 2011 Dec 7.

  PMID: 22160379 BACKGROUND

• Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007 Mar 15;109(6):2571-8. doi: 10.1182/blood-2006-01-024703. Epub 2006 Nov 21.

  PMID: 17119113 BACKGROUND

• Wu M, Hau PM, Li L, Tsang CM, Yang Y, Taghbalout A, Chung GT, Hui SY, Tang WC, Jillette N, Zhu JJ, Lee HHY, Kong EL, Chan MSA, Chan JYK, Ma BBY, Chen MR, Lee C, To KF, Cheng AW, Lo KW. Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers. Nat Commun. 2024 May 3;15(1):3729. doi: 10.1038/s41467-024-48031-8.

  PMID: 38702330 BACKGROUND

• Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi Y, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Wang S, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Luo X, Wang X, Tang X, Feng H, Yao S, Keegan P, Xu RH. Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial. JAMA. 2023 Nov 28;330(20):1961-1970. doi: 10.1001/jama.2023.20181.

  PMID: 38015220 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections

Interventions

Valganciclovir; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Hai-Qiang Mai, MD,PhD

  Sun Yat-sen Universitty Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiu-Yan Chen, MD,PhD

CONTACT

86-20-87343380; chenqy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 24, 2025
• Study Start: August 19, 2025
• Primary Completion (Estimated): August 18, 2026
• Study Completion (Estimated): August 18, 2031
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)