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

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.