Advanced malignant solid tumor
Conditions
Interventions
Dose Escalation phase:Universal solid tumor-specific antigen mRNA therapeutic vaccine(circFAM53B mRNA vaccine)
Dose Expansion phase:Universal solid tumor-specific antigen mRNA therapeutic vaccine(circFAM53B mRNA vaccine)
Sponsors
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily join the study, sign the informed consent form, and are willing and able to comply with the study protocol; 2. Gender is not limited, age is over 18 years old; 3. Expected survival >= 3 months; 4. Patients with histologically or cytologically confirmed unresectable or metastatic advanced solid malignancies, including but not limited to pancreatic malignancies, breast cancer, non-small cell lung cancer, melanoma, colorectal cancer, etc.; 5. For those who can obtain sufficient amount of fresh tumor tissue or paraffin tissue section by needle biopsy or surgery before treatment, the expression of circFAM53B-219aa from formalin-fixed paraffin-embedded (FFPE) is confirmed by RT-qPCR analysis/immunohistochemical staining. 6. HLA genotyping assay (using PCR-SBT sanger sequencing with polymerase chain reaction-direct sequencing (PCR-SBT) and typing with reference to IMGT/HLA database or PCR with specific primers or NGS technology), and then using pre-test models such as NetMHCpan and MHCflurry to predict tumor-specific circFAM53B-39aa and HLA-I (HLA-A, - B and -C) molecules and binding power, including HLA typing patients with rank value =1.5×10^9/L; • Platelet count (PLT) >=75×10^9/L; • Hemoglobin (Hb) >= 90 g/L; b) Liver function tests: AST, ALT, and alkaline phosphatase =50%; f) Pulmonary function tests: FEV1>=60%. 11. Non-surgically sterilized patients of childbearing age must agree to use at least one medically approved contraceptive measure (such as intrauterine device, birth control pills, or condoms) for contraception during the study treatment period and within 1 year after the end of the study treatment period; Non-surgically sterilized female patients of childbearing age must have a negative serum HCG test within 7 days prior to cell injection. 12. The patient has recovered from adverse reactions caused by previous treatment (CTCAE 5.0<=1) or can meet the detection values specified in the trial protocol (except for second-degree peripheral neuropathy, alopecia, cutaneous vitiligo/hypothyroidism controlled by hormone replacement therapy, and type I diabetes mellitus with good insulin control, and irreversible toxicity events that are judged by the investigator not to worsen by the vaccine).
Exclusion criteria
Exclusion criteria: 1. Subject has active infection requiring systemic treatment; 2. Patients with uncontrollable tumor-related pain as judged by the investigator. Subjects requiring analgesic medication must already have a stable analgesic regimen before enrollment, and symptomatic lesions suitable for palliative radiotherapy should be treated before enrollment; 3. Patients with severe cardiac disease or discomfort who are expected to be unable to tolerate chemotherapy, including but not limited to: fatal arrhythmias or higher grade atrioventricular block, unstable angina, clinically significant valvular heart disease, transmural myocardial infarction on electrocardiogram, and uncontrolled hypertension; 4. Received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before enrollment, or is participating in any interventional drug clinical trial; 5. Pregnant or lactating women. 6. Any active autoimmune disease, history of autoimmune disease, or disease requiring treatment with systemic steroid hormones or immunosuppressive medications (> 10 mg/day of prednisone or equivalent). Hormone replacement therapy (eg, thyroxine, insulin, or physiologic steroid hormones used to replace the treatment of adrenal or pituitary insufficiency) is allowed. 7. History of congenital or acquired immunodeficiency (e.g., positive HIV serotest). 8. Those who have active tuberculosis infection within 1 year before enrollment, or those who have a history of active tuberculosis infection more than 1 year ago but have not received formal treatment. 9. Patients with active hepatitis B or C. Patients who are positive for HBsAg or HBcAb can participate in this study if their HBV DNA test is less than the lower limit of normal detection in their research center. Patients with positive HCV antibody can participate in this study if the HCV RNA test is less than the lower limit of the normal value of the test at the research center. Carriers participating in the study need to arrange antiviral treatment as appropriate, and regular review during the study period for quantitative testing of nucleic acid copy number. 10. Active syphilis. 11. Vaccination of any form within 4 weeks prior to enrollment or anticipation of need for vaccines during the study. 12. Patients who have received prior allogeneic bone marrow transplantation or solid organ transplantation. 13. History of allergic reactions to the drugs to be used in the study, including but not limited to mRNA vaccines, toripalimab, or any component thereof. 14. Is using drugs that are prohibited from concomitant use with the trial drug (systemic corticosteroid therapy, live vaccines, etc.) unless the use of the drug is stopped 7 days before enrollment. 15. Other conditions assessed by the investigator that may affect the safety and compliance of the subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD);Dose-Limiting Toxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete);Determination and effects of antigen-specific T cells in peripheral blood;Progression Free Survival (PFS); | — |
Countries
China
Contacts
Public ContactErwei Song
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Outcome results
None listed