Trial Title:
Application of mRNA Immunotherapy Technology in Epstein-Barr Virus-related Refractory Malignant Tumors
NCT ID:
NCT05714748
Condition:
Malignant Tumors
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
mRNA vaccine
EBV
malignant tumor
immunotherapy
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
EBV mRNA vaccine
Description:
With 20ug as the starting point, the dose was increased using a dose escalation scheme.
Each subject only received one corresponding dose, and intramuscular injection was
administered again every 7 days, and after 4 doses, the 5th dose was given after 1 month
interval
Arm group label:
Treatment Cohort
Summary:
The purpose of this study is to evaluate the efficacy and safety of mRNA vaccine for the
EBV-positive Advanced Malignant Tumors.
Detailed description:
Epstein-Barr virus (Epstein-Barr virus), also known as human herpesvirus type 4, has an
infection rate of over 90% in the population. The global disease burden caused by EBV
infection is enormous, and it was one of the first human cancer viruses to be identified.
Prophylactic EBV vaccines have the potential to significantly reduce the incidence or
severity of EBV-associated diseases. Epstein-Barr virus is associated with a variety of
tumors of epithelial and lymphoid origin, such as Burkitt's lymphoma, Hodgkin's lymphoma,
nasopharyngeal carcinoma of epithelial origin, and some gastric cancers.
Vaccination is the most effective way to prevent EBV infection. In 1973, Epstein and
Achong first proposed the basic principle of developing a vaccine against Epstein-Barr
virus. However, more than 40 years later, there is still no approved EBV vaccine.
Therefore, it is urgent to develop new drugs for the treatment of EBV. EBV usually lurks
in human normal epithelial cells and B lymphocytes, shuttles between B lymphocytes and
epithelial cells, and spreads continuously in the human body[2], leading to the
recurrence of malignant tumors such as nasopharyngeal carcinoma, gastric cancer, and
lymphoma with transfer. It can be seen that the development of therapeutic drugs that
directly target EBV is expected to achieve better therapeutic effects on EBV-related
malignant tumors. At present, new biological treatment strategies targeting EBV have
shown good therapeutic potential in nasopharyngeal carcinoma, infectious mononucleosis,
lymphoma and other EBV-related diseases in the clinical trial stage, including viral
vector vaccines, DC or CAR -T cell therapy. At present, the virus vector preparations
targeting EBV include Ankara vaccinia virus and adenovirus. These viruses have safety
risks of integrating into the host genome and causing genome mutations in patients. The
DC (Dendritic cell) or CAR-T cell therapy strategy targeting EBV is complicated to
operate, takes a long time, is difficult to control quality, is difficult to produce on a
large scale, and has high production costs. In conclusion, the design strategy of the
above-mentioned new biological therapy still has a high risk of difficult clinical or
market transformation; therefore, it is necessary to develop new therapeutic biological
agents targeting EBV.
mRNA vaccines are a promising new approach to cancer. Its working principle is: introduce
the mRNA encoding the antigen into the cells of the body (especially the
antigen-presenting cells), synthesize the antigen protein or polypeptide through the
expression system of the host cell, activate cellular immunity and humoral immunity, and
achieve the purpose of highly effective anticancer[ 13]. The mRNA does not need to enter
the nucleus, it can be translated in the cytoplasm, and the effect is rapid; there is no
risk of integration into the host genome, and it will be automatically degraded in the
body, which is safe. Compared with traditional protein/polypeptide preparations, mRNA
nucleic acid has no problems such as antigen conformation change and degradation, and has
the advantages of long-term expression and persistent presentation of antigen; at the
same time, it can simulate the natural infection process of the virus to activate the
immune system and stimulate more Strong immune response; in addition, the production of
mRNA preparations is simple and the synthesis is fast. Different mRNA preparations can be
prepared using the same production steps and facilities, saving production costs. It is
considered to be a new type of nucleic acid preparation with good clinical application
prospects.
Based on the previous work, this project intends to carry out the research on new
immunotherapy technology of "targeting EB virus mRNA nucleic acid to treat EBV-related
malignant tumors". At present, there is no similar treatment method or product report in
the world, which is very innovative and advanced. Therefore, this project intends to
carry out phase I clinical research on the basis of previous research, in order to obtain
a therapeutic candidate vaccine targeting EBV with independent intellectual property
rights.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients: ≥18 years old and ≤70 years old.
2. Patients with EBV-positive advanced malignant tumors after failure of second-line
standard therapy.
3. ECOG physical condition score: 0-1 point.
4. Expected survival period ≥ 3 months.
5. The main organs are in good function, that is, the relevant inspection indicators
within 14 days before randomization meet the following requirements:
1. Blood routine examination: hemoglobin ≥ 90g/L and neutrophil count > 1.5×109/L
and platelet count ≥ 80×109/L.
2. Biochemical examination: total bilirubin≤1.5×ULN (upper limit of normal value),
blood alanine aminotransferase (ALT) or blood aspartate aminotransferase
(AST)≤2.5×ULN. if there is liver metastasis, ALT or AST≤5×ULN. Endogenous
creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula).
3. Cardiac Doppler ultrasound evaluation: left ventricular ejection fraction
(LVEF) ≥ 50%.
6. Sign the written informed consent
1. Subjects must sign and date the EC-approved written informed consent in
accordance with the guidelines of the competent authority and the research
institution. Informed consent must be signed prior to any protocol-related
procedures that are not part of the subject's routine medical care.
2. Subjects must be willing and able to comply with the scheduled visits,
treatment plans, laboratory tests, and other requirements of the study.
Exclusion Criteria:
Patients who meet any of the following criteria cannot be enrolled:
1. Participated in other drug clinical trials within 4 weeks;
2. The patient has a history of other tumors, unless it is cervical cancer in situ,
treated skin squamous cell carcinoma or bladder epithelial tumor or other malignant
tumors that have received radical treatment (at least 5 years before enrollment);
3. There are clinical symptoms or diseases of the heart that cannot be well controlled,
such as: heart failure above NYHA grade 2, unstable angina, myocardial infarction
within 1 year, clinically significant supraventricular or ventricular arrhythmia
requiring treatment or intervention of patients.
4. For female subjects: pregnant or lactating women.
5. Patients have active pulmonary tuberculosis, bacterial or fungal infection (≥2
grades of NCI-CTCAE 5.0); HIV infection, active HBV infection, HCV infection.
6. Those who have a history of psychotropic drug abuse and cannot quit or have mental
disorders;
7. The subject has any active autoimmune disease or has a history of autoimmune disease
(such as the following, but not limited to: uveitis, enteritis, hypophysitis,
nephritis, hyperthyroidism, hypothyroidism; the subject suffers from Subjects with
vitiligo or asthma that had been completely remitted in childhood and who did not
require any intervention in adulthood could be included; subjects with asthma
requiring medical intervention with bronchodilators could not be included).
8. Any abnormalities or permanent body art (such as tattoos) at the inoculation site
that, in the opinion of the investigator, would prevent observation of local
reactions at the inoculation site.
9. Patients who have been vaccinated with mRNA drugs.
10. Have participated in clinical trials involving lipid nanoparticles (one of the
components of the vaccine in this study).
11. There are contraindications for intramuscular injection
12. History of drug abuse or known medical, psychological or social conditions, such as
history of alcohol or drug abuse.
13. Known allergy, hypersensitivity or intolerance to the research vaccine (including
any excipients). There is a history of severe allergy to any drug, food, or
vaccination, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea,
allergic purpura, thrombocytopenic purpura, local allergic necrotic reaction (Arthus
reaction), etc.
14. From the screening period to 12 months after the full injection of the drug, the
female subject has a pregnancy plan or the partner of a male subject has a pregnancy
plan.
15. According to the investigator's judgment, there are concomitant diseases that
seriously endanger the patient's safety or affect the patient's completion of the
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Xingchen Peng
Phone:
+86 18980606753
Email:
pxx2014@scu.edu.cn
Start date:
November 18, 2022
Completion date:
January 2025
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05714748
