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

Обзор

Epstein-Barr virus (EBV) is an important tumor-associated virus. In 1997, the World Health Organization (WHO) officially classified EBV as a Group 1 carcinogen, as it is implicated in the pathogenesis of various epithelial malignancies and multiple types of lymphomas. Epithelial malignancies associated with EBV infection include nasopharyngeal carcinoma (NPC), gastric cancer, colorectal cancer, breast cancer, cervical cancer, prostate cancer, and oral cancer, among others. Currently, optimal therapeutic strategies for EBV-associated tumors remain lacking, particularly in patients with recurrent, metastatic, or refractory disease. Furthermore, although EBV infection plays a significant role in the development and progression of EBV-positive tumors and may influence patient prognosis, there are currently no precision therapeutic approaches specifically targeting EBV-positive lymphomas. Thus, treatment options for this patient population warrant further attention. EBV mRNA vaccine is a therapeutic vaccine based on messenger RNA (mRNA) targeting antigens related to EBV. This clinical trial aims to evaluate the safety, tolerability, immunogenicity, and preliminary antitumor activity of EBV mRNA vaccine in patients with advanced EBV-positive malignant tumors, thereby providing a scientific basis for subsequent clinical development.

Вмешательства

• Биопрепарат EBV mRNA vaccine
  EBV mRNA vaccine
• Биопрепарат Immune Checkpoint Inhibitors, ICIs
  Immune Checkpoint Inhibitors, ICIs

Первичные конечные точки

• Dose limiting toxicity (DLT) [Срок оценки: During one year after initial treatment]
• Safety: Type, frequency, and severity of treatment-related adverse events [Срок оценки: During one year after initial treatment]

Вторичные конечные точки (4)

• Objective response rate (ORR) [Срок оценки: During one year after initial treatment]
• Disease control rate (DCR) [Срок оценки: During one year after initial treatment]
• Progression-free survival (PFS) [Срок оценки: During one year after initial treatment]
• Survival rate (1-year, 2-year) [Срок оценки: During one and two years after initial treatment]

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07101536 · EBV-mRNA-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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