Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001) (NCT06141369) | Clinical Trial Compass
RecruitingNot Applicable
Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)
China21 participantsStarted 2024-01-13
Plain-language summary
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).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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);
What they're measuring
1
Maximum tolerated dose (MTD) or Dose-limiting toxicity (DLT).If MTD is not reached, Biologically Effective Dose (BED)tumor neoantigen.
Timeframe: At the end of cycle 1(each cycle is 21 days)
2
Incidence of treatment-related adverse events.
Timeframe: At the end of cycle 1(each cycle is 21 days)
Trial details
NCT IDNCT06141369
SponsorShanghai Jiao Tong University School of Medicine
✓. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1;
Exclusion criteria
✕. 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
✕. Patients with clinically symptomatic brain metastases, spinal cord compression, carcinomatous meningitis, or other evidence indicating that the patient's brain or spinal cord metastases are not controlled, and are deemed unsuitable for enrollment by the investigator;
✕. In the past 2 years, there have been known other malignant tumors that are progressing or require active treatment (except for non-melanoma skin cancer, superficial bladder cancer, and cervical carcinoma in situ that have been cured by radical surgery);
✕. Have a history of interstitial lung disease (ILD) or pulmonary interstitial fibrosis;
✕. Have a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: a) Have severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, II-III degree atrioventricular block; corrected QTc interval male \> 450 milliseconds, female \> 470 milliseconds, b) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first administration, c) New York Heart Association (NYHA) ≥ III grade heart failure or left ventricular ejection fraction (LVEF) \<50%.