Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)
Treatment of advanced endocrine tumors, including adrenal corticocarcnioma (ACC), medullary thyroid carcinoma (MTC), thymic neuroendocrine tumor and pancreatic neuroendocrine tumor is challenging. Previous genomic profiling studies showed they presented a number of somatic mutations. The tumors Individualized mRNA neoantigen vaccine provide a promising solution since a significant portion of these tumors showed high quality of tumor specific neoantigen. The primary objective is to observe and evaluate the safety and tolerability of individualized mRNA neoantigen vaccine (mRNA-0523-L001) for the treatment of advanced endocrine tumors, failure of standard treatment or no standard treatment currently available. The secondary objective is to observe the preliminary efficacy of mRNA-0523-L001 for the treatment of advanced endocrine tumors, failure of standard treatment or no standard treatment currently available, including: 1. Neoantigen-specific CD4+ and CD8+ T lymphocyte responses induced by mRNA-0523-L001; 2. Objective response rate (ORR) and disease control rate (DCR) of tumors; 3. Progression-free survival (PFS).
• The subjects voluntarily sign the written informed consent form and can comply with the visits and related procedures specified in the protocol;
• The subjects are 18 years old or older, regardless of gender;
• Patients with advanced endocrine tumors confirmed by histology or cytology in the past 6 months (including medullary thyroid carcinoma, thymic carcinoma and adrenal cortical carcinoma, etc.), who have failed standard treatment or have no standard treatment available;
• No HLA-related genes or chromosomal regions with copy number variations (CNVs) or loss of heterozygosity (LOH) were detected by gene sequencing;
• They have advanced or metastatic lesions confirmed by immunohistochemistry, and have frozen tissue/cells sufficient for WES and RNAseq sequencing, and after bioinformatics analysis, they predict at least one antigen that is effectively presented by their own HLA, such as KRAS or TP53 mutations and corresponding HLA typing, see 1.4 for the rationale of the topic.
• Expected survival ≥ 4 months;
• According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they have at least one measurable lesion, which should not have received local treatment such as radiotherapy (lesions in the previous radiotherapy area, if confirmed to have progressed, can also be selected as target lesions);
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1;
• They have not used granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion or platelet transfusion within 14 days before the examination.
⁃ Subjects of childbearing potential (male and female) who meet the inclusion criteria must agree to use reliable contraception methods (hormonal or barrier methods or abstinence) during the trial and for at least 90 days after the last administration; women of childbearing age must have a negative blood pregnancy test within 7 days before the first administration.
⁃ Virology test: No CMV, EBV, HIV, HBV, HCV, syphilis infection (only at baseline)