EBV associated malignant tumors
Conditions
Interventions
Intervention group 1 (mRNA monotherapy - Dose escalation stage):EBV vaccine, 25ug
Intervention group 2 (mRNA monotherapy - Dose escalation stage):EBV vaccine, 50ug
Intervention group 3 (mRNA monotherapy - Dose escalation stage):EBV vaccine, 100ug
Intervention group 4 (mRNA monotherapy - Dose expansion stage):EBV vaccine, 100ug
Intervention group 5 (mRNA-based combination therapy stage):EBV vaccine + Immune checkpoint inhibitors
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Phase 1: Monotherapy Study of mRNA Vaccine? ?1. Male or female patients aged >=18 years; 2. Patients with EBV-positive advanced-stage tumors (including EBV-associated nasopharyngeal carcinoma, NK/T-cell lymphoma, and EBV-associated gastric cancer) who have failed at least two lines of standard therapy (confirmed by EBER FISH positivity in tumor tissue); 3. ECOG performance status score: 0–2; 4. Estimated life expectancy >=3 months; 5. Adequate major organ function, with all screening laboratory values meeting the following criteria within 14 days prior to treatment: ?(1) Hematology:?? Hemoglobin >=90 g/L (no blood transfusion within 14 days); Absolute neutrophil count >1.5×10^9/L; Platelet count >=80×10^9/L; ?(2) Biochemistry:?? Total bilirubin =60 mL/min (calculated by Cockcroft-Gault formula); ?(3) Cardiology:?? Left ventricular ejection fraction (LVEF) >=50% (by echocardiography); (4) If the investigator determines that any abnormal values are due to disease progression, patients may still be enrolled at their discretion. 6. Written informed consent: ?(1) Patients must sign an IRB-approved informed consent form (with date) in accordance with regulatory and institutional guidelines before any protocol-specific procedures (beyond routine medical care) are performed; ?(2) Patients must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and all other study requirements. Phase 2: Combination Therapy Study of mRNA Vaccine 1. Male or female patients aged >=18 years; 2. Patients with histologically or cytologically confirmed advanced or refractory EBV-positive tumors (including but not limited to nasopharyngeal carcinoma, gastric cancer, lymphoma, etc.) who have failed at least one line of systemic therapy, with EBER positivity in tumor tissue detected by in situ hybridization (ISH or FISH); 3. At least one measurable or evaluable target lesion; 4. Eastern Cooperative Oncology Group (ECOG) performance status score: 0–2; 5. Estimated life expectancy >=3 months; 6. Adequate major organ function, with all screening laboratory values meeting the following criteria within 14 days prior to first dose or within 5 half-lives of the drug (whichever is shorter): (1) Hemoglobin >=80 g/L; absolute neutrophil count >=1.0×10^9/L; platelet count =80×10^9/L (no use of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, recombinant human erythropoietin, or recombinant human thrombopoietin within the specified time window; no component blood transfusion within 7 days prior to first dose); (2) Total bilirubin =50 mL/min (calculated by Cockcroft-Gault formula); (5) Prothrombin time (PT) and international normalized ratio (INR) =45% (by echocardiography); (7) If the investigator determines that any abnormal values are due to disease progression, patients may still be enrolled at their discre
Exclusion criteria
Exclusion criteria: Phase 1: Monotherapy Study of mRNA Vaccine 1. Participation in other clinical drug trial within the past 4 weeks; 2. History of other malignancies, except for cervical carcinoma in situ, treated cutaneous squamous cell carcinoma or urothelial tumors, or other malignancies that have undergone curative treatment (with disease-free survival of at least 5 years prior to enrollment); 3. Uncontrolled cardiac symptoms or diseases, such as: NYHA Class II or higher heart failure, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; 4. Female subjects who are pregnant or breastfeeding; 5. Patients with active tuberculosis, bacterial or fungal infections (>=Grade 2 per NCI-CTCAE 5.0), active HIV infection, active HBV infection, or HCV infection; 6. History of psychotropic drug abuse with inability to abstain or presence of psychiatric disorders; 7. Subjects with any active autoimmune disease or history of autoimmune diseases (e.g., but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism); subjects with vitiligo or childhood asthma that has been completely resolved without any intervention in adulthood may be included; subjects requiring bronchodilators for medical management of asthma are excluded; 8. Any abnormalities at the injection site or permanent body art (e.g., tattoos) that, in the investigator's judgment, may interfere with observation of local injection-site reactions; 9. Patients who have previously received mRNA-based drugs; 10. Participation in clinical trials involving lipid nanoparticles (a component of the study vaccine); 11. Contraindications to intramuscular injection; 12. History of drug abuse or known medical, psychological, or social conditions such as alcoholism or drug addiction; 13. Known allergy, hypersensitivity, or intolerance to the study vaccine (including any excipients); history of severe allergic reactions to any drug, food, or vaccine, including but not limited to: anaphylactic shock, anaphylactic laryngeal edema, anaphylactic dyspnea, allergic purpura, thrombocytopenic purpura, localized allergic necrotic reaction (Arthus reaction), etc.; 14. Female subjects with pregnancy plans from screening through 12 months after the final drug administration, or male subjects whose partners have pregnancy plans during this period; 15. Any concomitant disease that, in the investigator's judgment, poses a serious risk to patient safety or may affect the patient's ability to complete the study. Phase 2: Combination Therapy Study of mRNA Vaccine 1. History of other malignancies, except for adequately treated and non-recurrent within 5 years prior to screening basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal mucosal carcinoma, which the investigator deems eligible for inclusion; 2. Central nervous system (CNS) tumors or CNS metastases; 3. Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage; hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or worse cirrhosis; 4. Known invasive NK-cell leukemia or NK lymphoblastic leukemia/lymphoma; or hemophagocytic syndrome; 5. Known clinically significant uncontrolled cardiac symptoms or diseases, such as: New York Heart Association (NYHA) Class II o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities (DLTs) and their incidence rates (Dose escalation stage);Safety (Dose escalation stage);Safety (Dose expansion stage); | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Disease control rate, DCR;Duration of Response;Progression-free survival, PFS;Overall Survival, OS / 1-year survival rate;Immunogenicity; | — |
Countries
China
Contacts
Public ContactPeng Xingchen
West China Hospital of Sichuan University
Outcome results
None listed