Clinical Study for the Therapeutic Efficacy and Safety of a Personalized and AI-Quantum Mechanics Based and Molecular Modeled Cancer Specific Neoantigenic Vaccine, the TamavaqTM NeoVaccine in Patients With Newly Diagnosed Glioma.

Biogenea Pharmaceuticals Ltd.2 个研究点分布在 1 个国家目标入组 29 人开始时间: 2025年7月1日最近更新: 2025年12月8日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 29
试验地点: 2
主要终点: TAMAVAQ Vaccine Safety Analysis

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Gliomas are a heterogeneous group of tumors arising from glial cells in the central nervous system and are associated with poor prognosis and significant morbidity. The most aggressive form, glioblastoma multiforme (GBM), remains particularly challenging to treat, often exhibiting resistance to conventional therapies such as chemotherapy and radiation. The average survival for patients with GBM is approximately 15 months, underscoring the urgent need for novel therapeutic strategies that can improve outcomes. Malignant gliomas are the most common primary brain cancer diagnosed and still carry a poor prognosis despite aggressive multimodal management. Despite the continued advances in immunotherapy for other cancer types, however, there remain no FDA approved immunotherapies for cancers such as glioblastoma. Neoantigen vaccines are a form of immunotherapy involving the use of DNA, mRNA, and proteins derived from non-synonymous mutations identified in patient tumor tissue samples to stimulate tumor-specific T-cell reactivity leading to enhance tumor targeting. Up to and including the current time, we have only nascent understandings, at the molecular and submolecular level, of how immunity is generated and maintained. As a result, we do not have fundamental mechanistic understandings of vaccine:antigen interactions, of vaccine-directed and initiated routes of immunity, nor how, through adjuvants and changes in our biologic environment (such as the intestinal microbiome), we might direct such immune responses. In particular, in the field of vaccinology we have few collaborations between biology, physics, and chemistry...or what has been termed "convergence science"...but particularly from physics and the field of quantum mechanics. Biophysics led to quantum biology and quantum immunology reflecting quantum dynamics within living systems and their evolution. Unfortunately, despite the seismic influence of immunotherapy on oncology today, there remain no FDA approved immunotherapies for GBM due to the lack of efficacy observed in several randomized clinical trials. The TAMAVAQ approaches enable a quantitative understanding of immune response kinetics following neoantigen-based peptide vaccine treatment. Insights gained from challenges can be used to design better vaccines and evaluate the potential candidate vaccines in silico. The TAMAVAQ models also can guide such decisions on treatment regimens such as dosing and infusion frequencies.

详细描述

Quantum Vaccinomics for the Generation of the TAMAVAQ personalized neoantigenic vaccines.

The personalized neoantigen vaccines will be prepared based on the analysis of whole-exome sequencing (WES) and RNA-seq data generated from fresh-frozen tumours or tumours that will be available as formalin-fixed paraffin-embedded (FFPE) tissue, obtained at the time of diagnostic resection. WES of normal tissue will be generated from autologous PBMC DNA. Patient HLA allotype will be assessed using standard class I and class II PCR-based typing (BWH Tissue Typing Laboratory). Coding mutations will be identified and personal neoantigens will be predicted based on binding affinity analysis to individual HLA alleles using class I MHC binding prediction tools with a cut-off of predicted IC50 < 500 nM for selected epitopes. Quantum Circuit platforms for the identification of immunological quantum and design of TAMAVAQ's NeoVaccine consisted of Druggable Immunodominant and Immunogenic Neo-epitopic Peptides will be incorporated in this clinical study. Candidate and Prioritized Neo-epitopic Peptides are identified using systems biology integration of omics dataset combined with Big Data analytics and machine learning. Then, the immunodominant quantized peptide will be identified by using in silico algorithms and HLA epitope mapping and binding domains involved in each one Glioma Patient's Drug-DNA-Protein-protein interactions.

This clinical trial provides an AI-QMMM method for the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens exploring their current status, inherent challenges, and clinical translation potential against Glioma medical conditions.

Enhanced Targeted Therapy**:- The TAMAVAQ vaccine specifically targets neoantigens unique to glioma cells, potentially leading to a more effective immune response while sparing healthy cells. This specificity may reduce collateral damage associated with traditional cancer therapies.

Immune System Activation**:The TAMAVAQ personalized vaccine is designed to stimulate the patient's immune system, enhancing its ability to recognize and attack glioma cells. This activation can lead to a more robust and sustained anti-tumor response.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•1. **Age**:
•Patients must be aged 18 years or older.
•signed inform consent;
•patients with recurrent malignant glioma; have received surgery, radiotherapy, chemotherapy;
•patients' tumor tissue should have a high mutation load(>10 TMB); be genetically unstable; at least have 10 neoantigens;
•should be able to provide tumor tissue and peripheral blood for sequencing and flow cytometry analysis;
•at least three months post last operation; one month after the completion of the last anti-drug therapy or radiotherapy;
•have not received any immunotherapy;
•at least have one measurable lesion;
•KPS >60;
•estimated survival > 3 months
•patients should have adequate organ and bone marrow function;
•**Diagnosis**:
•Histologically confirmed diagnosis of glioma, including:
•Glioblastoma multiforme (GBM, WHO grade IV)
•Anaplastic astrocytoma (WHO grade III)
•Diffuse astrocytoma (WHO grade II)
•Other gliomas (e.g., oligodendroglioma, mixed glioma) confirmed by pathology.
•3. **Measurable Disease**:
•Presence of measurable disease, defined as at least one tumor lesion that can be accurately assessed by imaging techniques (e.g., MRI) according to RECIST criteria.
•4. **Performance Status**:
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, indicating that patients are fully active, restricted in physically strenuous activity, or unable to work but able to care for themselves.
•5. **Adequate Organ Function**:
•Laboratory results must indicate adequate organ function, including:
•Hematological parameters: Hemoglobin ≥ 9 g/dL, white blood cell count ≥ 3,000 cells/mm³, platelet count ≥ 100,000 cells/mm³.
•Liver function tests: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 2.5 times the upper limit of normal (ULN) (or ≤ 5 times the ULN if there is liver involvement).
•Renal function: Serum creatinine ≤ 1.5 times the ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min.
•6. **Informed Consent**:
•Provision of written informed consent by the patient or their legally authorized representative, indicating understanding of the study procedures, potential risks, and benefits.
•7. **No Prior Treatment with Certain Therapies**:
•Patients must not have received prior treatment with immune checkpoint inhibitors or other experimental immunotherapies that may interfere with the study outcomes.
•8. **Ability to Comply with Study Procedures**:
•Patients must be able to comply with all study procedures, including follow-up visits and assessments, as determined by the investigator.
•9. **No Significant Cognitive Impairment**:
•Patients must not have significant cognitive impairment or psychiatric disorders that would compromise their ability to provide informed consent or adhere to the study protocol.
•These inclusion criteria are designed to ensure that the study population for this glioma targeted personalized neoantigen vaccine clinical trial is suitable for participation, allowing for the collection of meaningful data regarding the safety and efficacy of the investigational treatment. By clearly defining eligibility, the trial aims to target patients who are most likely to benefit from this AI-QMMM inspired therapeutic approach.

排除标准

•**Previous Treatments**:
•Patients who have received prior treatment with immune checkpoint inhibitors, other cancer vaccines, or experimental immunotherapies that may interfere with the study outcomes.
•2. **Active Autoimmune Diseases**:
•Patients with active autoimmune diseases or chronic inflammatory conditions requiring systemic treatment (e.g., rheumatoid arthritis, lupus, multiple sclerosis).
•3. **Pregnancy or Breastfeeding**:
•Pregnant or breastfeeding women, as the effects of the vaccine on fetal development or breastfeeding infants are not yet established.
•4. **Other Malignancies**:
•Patients with any other malignancy within the past 5 years, except for non-melanoma skin cancer or localized prostate cancer that is not currently active.
•5. **Uncontrolled Medical Conditions**:
•Patients with uncontrolled medical conditions, including but not limited to:
•Cardiovascular disease (e.g., recent myocardial infarction, severe heart failure).
•Uncontrolled infections (e.g., HIV, active hepatitis B or C).
•Severe chronic lung disease.
•6. **Significant Cognitive Impairment**:
•Patients with significant cognitive impairment or psychiatric disorders that would limit their ability to provide informed consent or comply with study procedures.
•7. **Severe Allergies**:
•Patients with known hypersensitivity or severe allergic reactions to any component of the vaccine formulation or adjuvants used in the study.
•8. **Concurrent Participation in Other Clinical Trials**:
•Patients currently participating in other clinical trials involving investigational drugs or therapies that may interfere with the study outcomes.
•9. **History of Organ Transplant**:
•Patients who have received an organ transplant that requires ongoing immunosuppressive therapy.
•10. **Severe Comorbidities**:
•Patients with severe comorbid conditions that, in the opinion of the investigator, may compromise the safety of the patient or interfere with the assessment of the study endpoints. -

研究组 & 干预措施

Experimental: personalized vaccine patients with recurrent malignant gliomas enrolled into this arm

Experimental

Clinical event timeline and Dosing of TAMAVAQ VACCINES

Clinical event timeline for the patients who received at least one vaccine dose of (20-200)μg TAMAVAQ NeoVaccine, will be calculated from surgery until time of death due to progressive disease. Median progression-free survival (PFS) and overall survival (OS) will be also calculated respectively. Among enrolled patients, a median of (110-145) somatic single-nucleotide variants per tumour (range, 75-158) will be tested with a median of (58-63) coding mutations per tumour (range, 32-93) using whole-exome sequencing, and the expression of a subset of genes will be confirmed by RNA sequencing (RNA-seq) analysis. These included mutations commonly observed in glioblastoma that affect PTEN, RB1 and EGFR. No IDH1 or IDH2 mutations will be also tested. A median of 60.5-70,8 HLA binders (range, 30-163) with a half-maximum inhibitory concentration (IC50) < 500 nM will be predicted per tumour.

干预措施: Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced; (Biological)