The Application of mRNA Immunotherapy Technology in Refractory Malignancies Associated With Epstein-Barr Virus (EBV)

Inclusion criteria

Phase 1: Monotherapy Study of mRNA Vaccine

• Male or female patients aged ≥18 years;
• Patients with advanced Epstein-Barr virus (EBV)-positive tumors (e.g., nasopharyngeal carcinoma, NK/T-cell lymphoma, or gastric cancer) who have failed at least two lines of standard therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2;
• Estimated survival ≥3 months;
• Adequate major organ function;
• Additional inclusion criteria may be supplemented.

Phase 2: Combination Therapy Study of mRNA Vaccine

• Male or female patients aged ≥18 years at screening;
• Histopathologically confirmed recurrent or metastatic nasopharyngeal carcinoma (NPC) not amenable to local therapy, with documented failure of at least one prior platinum-containing chemotherapy regimen and PD-1/L1 immunotherapy;
• Positive for Epstein-Barr virus-encoded RNA (EBER) in tumor tissue;
• At least one measurable lesion per RECIST v1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2;
• Additional inclusion criteria may be supplemented.

Exclusion criteria

Phase 1: Monotherapy Study of mRNA Vaccine

• Participation in another clinical drug trial within the past 4 weeks;
• History of other malignancies, unless it is cervical carcinoma in situ, treated cutaneous squamous cell carcinoma or urothelial tumors, or other malignancies that have undergone curative treatment (at least 5 years prior to enrollment);
• Uncontrolled cardiac symptoms or diseases;
• Female subjects who are pregnant or breastfeeding;
• Active tuberculosis, bacterial or fungal infections; active HIV infection, active HBV infection, or HCV infection;
• Additional exclusion criteria may be supplemented.

Phase 2: Combination Therapy Study of mRNA Vaccine

• History of other primary malignancies within 3 years prior to the first dose, excluding adequately treated tumors with no evidence of recurrence for at least 2 years;
• Known clinically significant uncontrolled cardiac symptoms or diseases;
• Presence of central nervous system disorders (e.g., epilepsy, severe cerebrovascular stenosis), or history of cerebrovascular accident (e.g., stroke) or other cerebrovascular events within 6 months prior to screening, or other conditions (including psychiatric disorders) with overt neurological symptoms;
• Known history of interstitial pneumonia or high suspicion of interstitial pneumonia; or presence of pulmonary abnormalities that may interfere with the detection or management of suspected drug-related pulmonary toxicity during the trial;
• Any active autoimmune disease or history of autoimmune diseases;
• Additional exclusion criteria may be supplemented.