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;
Received chemotherapy, hormone therapy, traditional Chinese medicine with anti-tumor indications or other anti-tumor treatments within 4 weeks before the first administration (for mitomycin and nitrosourea, the last administration was within 6 weeks before the first administration of this study drug), or within 5 half-lives of immunotherapy or molecular targeted therapy;
Received other major surgery other than diagnosis or biopsy within 4 weeks before the first administration, or expected to receive major surgery during the study;
Patients who have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past, or plan to receive organ transplantation during this study;
Patients who have received other tumor vaccines or cell therapies in the past; Medical condition
Single group
individualized mRNA neoantigen vaccine (mRNA-0523-L001)
Biological/VaccineIndividualized mRNA neoantigen vaccine (mRNA-0523-L001) will be injected intramuscularly every 21 days for 9 cycles. Dose escalation will be administered in 3 patients. 18 additional patients will be recruited and administered at the maximum tolerated(MTD) dose for all nine cycles. Injection of mRNA-0523-L001 will continue if an objective response is observed until the discontinuation criteria are met.
Maximum tolerated dose (MTD) or Dose-limiting toxicity (DLT).If MTD is not reached, Biologically Effective Dose (BED)tumor neoantigen.
The highest dose of a drug or treatment that does not cause unacceptable side effects.
Incidence of treatment-related adverse events.
According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).
Reaction of antigen-specific T cells in peripheral blood.
mRNA-0523-L001 personalized tumor vaccine induces neoantigen specific CD4+and CD8+T lymphocyte responses.
Objective tumor response rate (ORR)
ORR calculates the ratio of the number of patients whose best response is complete remission (CR) or partial remission (PR) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted.
Disease control rate (DCR)
DCR calculates the ratio of the number of patients whose best response is complete remission (CR), or partial remission (PR), or stable disease (SD) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted.
Progressive free survival (PFS)
Progression-free Survival of Personalized mRNA Tumor Vaccine.
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