EBV-associated Tumors
Conditions
Brief summary
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.
Interventions
BIOLOGICALEBV mRNA vaccine
EBV mRNA vaccine
BIOLOGICALImmune Checkpoint Inhibitors, ICIs
Immune Checkpoint Inhibitors, ICIs
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity (DLT) | During one year after initial treatment |
| Safety: Type, frequency, and severity of treatment-related adverse events | During one year after initial treatment |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) | During one year after initial treatment |
| Disease control rate (DCR) | During one year after initial treatment |
| Progression-free survival (PFS) | During one year after initial treatment |
| Survival rate (1-year, 2-year) | During one and two years after initial treatment |
Outcome results
None listed