NCT07138989

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

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Nasopharyngeal Cancinoma (NPC)

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-08-19
• Primary completion: 2026-08-18
• Completion: 2031-08-18
• First posted: 2025-08-24
• Last updated: 2025-08-24

Locations

1 site across 1 country: China