Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)

NCT06141369 | Recruiting DMC

• 1 other identifier: KY2023-161
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 1.Neoantigen-specific CD4+ and CD8+ T lymphocyte responses induced by mRNA-0523-L001;
2. 2.Objective response rate (ORR) and disease control rate (DCR) of tumors;
3. 3.Progression-free survival (PFS).

Conditions

Medullary Thyroid Cancer; Pancreatic Neuroendocrine Tumor; Thymic Neuroendocrine Carcinoma; Adrenal Cortical Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  At the end of cycle 1(each cycle is 21 days)

• Incidence of treatment-related adverse events.

  According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

  At the end of cycle 1(each cycle is 21 days)

Secondary Outcomes (4)

• Reaction of antigen-specific T cells in peripheral blood.

  At the end of cycle 1(each cycle is 21 days)

• Objective tumor response rate (ORR)

  At the end of cycle 1(each cycle is 21 days)

• Disease control rate (DCR)

  At the end of cycle 1(each cycle is 21 days)

• Progressive free survival (PFS)

  At the end of cycle 1(each cycle is 21 days)

Study Arms (1)

mRNA-0523-L001

EXPERIMENTAL

individualized mRNA neoantigen vaccine (mRNA-0523-L001)

Biological: individualized mRNA neoantigen vaccine (mRNA-0523-L001)

Interventions

individualized mRNA neoantigen vaccine (mRNA-0523-L001) BIOLOGICAL

Individualized 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.

mRNA-0523-L001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Virology test: No CMV, EBV, HIV, HBV, HCV, syphilis infection (only at baseline)

You may not qualify if:

• 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%.
• Other serious and/or uncontrollable diseases that may affect the subject's participation in this study, as determined by the investigator, including but not limited to: a) Have a history of severe drug allergy, or known to be allergic to any component of the tumor vaccine; or have had a severe allergic reaction to other monoclonal antibodies in the past, b) Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, c) Evidence of severe or uncontrolled liver or kidney disease, d) Poorly controlled hypertension, diabetes, etc., e) Patients with active ulcers or gastrointestinal bleeding f) Have a severe infection that requires intravenous infusion of antibiotics or hospitalization; or uncontrolled active infection within 4 weeks before the first administration, g) Have active syphilis infection.
• Participated in other clinical trials within 4 weeks before the first administration (except for screening failure);
• Currently receiving systemic use of corticosteroids (except for recent or current use of inhaled corticosteroids);
• Pregnant or lactating women; Laboratory and imaging examinations
• Imaging (CT or MRI) shows that the tumor invades the large blood vessels and has a tendency to bleed;
• Have clinically significant thyroid function abnormalities, and the investigator deems them unsuitable for enrollment;
• Active pneumonia was found in the screening chest CT scan;

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Ruijin hospital, Shanghai Jiao-Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

Related Publications (27)

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MeSH Terms

Conditions

Adrenocortical Carcinoma; Carcinoma, Medullary; Adenoma, Islet Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Adenoma; Pancreatic Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Central Study Contacts

Lei Ye

CONTACT

15201909962; lei_yelei@163.com

Luming Wu

CONTACT

13818707008; wulum@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: November 21, 2023
• Study Start: January 13, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)