Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

NCT07077616 | Recruiting Early Phase 1 DMC

• 2 other identifiers: Biogenea1Biogenea1979
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioma

Keywords

Personalised Vaccine; Neoantigenic Peptides; AI-designed; Machine Learning-predicted; Quantum Mechanics structured; Molecular Dynamics-modeled; Immunodominant Peptides

Outcome Measures

Primary Outcomes (5)

• TAMAVAQ Vaccine Safety Analysis

  The primary objective of this study is to determine the safety of TAMAVAQ in patients with glioblastoma and to determine if TAMAVAQ shows sufficient safety in these patients. The safety assessments outlined for the TAMAVAQ vaccine clinical trial are essential for ensuring participant well-being and monitoring the impact of the intervention. The primary outcomes assessed by this clinical study were safety and efficacy of the TAMAVAQ autologous neoantigenic vaccine products based on reported adverse events (AEs) and clinical response respectively. To evaluate the safety of a neoantigen cancer vaccine, the Investigators monitor for adverse events using standardized criteria like the Common Terminology Criteria for Adverse Events (CTCAE) and assess changes in blood, urine, and organ function. They also track health-related quality of life.The Investigators will use the CTCAE to grade and track adverse events (side effects) that occur during and after TAMAVAQ vaccination.

  From initiation of study treatment to 28 weeks post-vaccination

• Incidences of Advent Events and Severe Advent Events

  Safety oversight is a critical component of clinical trials, ensuring that participant safety is prioritized throughout the study. Below is an outline of the safety oversight mechanisms and procedures for an AI and quantum mechanics-based brain tumor targeted personalized neoantigenic peptide vaccine clinical trial. * The safety of the TAMAVAQ vaccines will be evaluated by analyzing the rate of Grade 1-3 Treatment Related Adverse Events (TRAEs). The specific adverse events to be monitored include: * \*\*Fever\*\* * \*\*Headache\*\* * \*\*Flu-like Symptoms\*\* * \*\*Lymphopenia\*\* * \*\*Injection Site Reactions\*\* * \*\*Vomiting\*\* * \*\*Diarrhea\*\* * By systematically reviewing data from multiple studies, the analysis aims to quantify the incidence of these adverse events and provide a comprehensive understanding of the TAMAVAQ vaccine's safety profile.This provides a standardized way to assess the severity and frequency of potential safety issues.

  From initiation of study treatment to 28 weeks post-vaccination

• Physiological Monitoring and Toxicity Analysis

  Physiological Monitoring: Changes in blood counts, urine analysis, liver and kidney function tests, and electrolyte and coagulation parameters are monitored before and after TAMAVAQ vaccination to detect any physiological abnormalities that could be related to the TAMAVAQ vaccine. This structured approach enhances the reliability of trial outcomes and contributes to the advancement of the TAMAVAQ personalized cancer therapies for glioma patients. Toxicity Analysis: The Investigators will evaluate the overall toxicity profile of the vaccine, considering the frequency and severity of adverse events.

  From initiation of study treatment to 28 weeks post-vaccination

• Gadolinium-enhanced MRI

  To evaluate the safety of the TAMAVAQ neoantigen vaccines in glioma patients using Gadolinium-enhanced MRI, the primary approach involves monitoring changes in tumor size and characteristics over time, specifically using the McDonald criteria. These criteria, applied to gadolinium (Gd)-enhanced T1-weighted images, assess tumor response based on the appearance of the pre-treatment MRI. Additionally, T2-weighted images and potentially other advanced MRI techniques like dynamic susceptibility contrast (DSC)-MRI will provide further insights into tumor progression, pseudoprogression, and immune activity. Gadolinium-enhanced T1-weighted images: These images are crucial for visualizing areas of increased vascular permeability, which often indicate tumor growth or recurrence.

  From initiation of study treatment to 28 weeks post-vaccination

• AI Techniques and Machine Learning Models for the TAMAVAQ's Safety Integration Analysis

  Data Cleansing \& Normalization: Handling heterogeneous data formats. Consider incorporating machine learning algorithms to improve the safety of the TAMAVAQ's vaccine neoantigen prediction and patient stratification based on historical data. * \*\*Natural Language Processing (NLP):\*\* Extract insights from unstructured clinical notes, glioma pathology reports. * \*\*Machine Learning Models:\*\* * Supervised learning for predicting TAMAVAQ's treatment safety outcomes. * Unsupervised clustering for TAMAVAQ's patient stratification. * \*\*Predictive Modeling:\*\* Identifying unstructured factors associated with TAMAVAQ's safety. * \*\*Meta-Analytic Framework:\*\* Combining effect sizes across studies to derive overall estimates. * Safety profile comparison with other Glioma targeted immunotherapies.

  From initiation of study treatment to 28 weeks post-vaccination

Secondary Outcomes (23)

• Revised Assessment in Neuro-Oncology (RANO) Criteria for measuring the effectiveness of TAMAVAQ treatments in glioma patients.

  From initiation of study treatment to 48 weeks post-vaccination

• Measurable Lesions and Macdonald Criteria

  From initiation of study treatment to 48 weeks post-vaccination

• MRI Advanced Imaging Techniques

  From initiation of study treatment to 48 weeks post-vaccination

• Perfusion Imaging (DSC, DCE, ASL)

  From initiation of study treatment to 48 weeks post-vaccination

• Diffusion Imaging (DTI, DKI)

  From initiation of study treatment to 48 weeks post-vaccination.

Other Outcomes (2)

• Patient-Reported Outcomes (PROs)

  From initiation of study treatment to 48 weeks post-vaccination

• Neurological Examination

  From initiation of study treatment to 48 weeks post-vaccination

Study Arms (1)

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.

Biological: Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;

Interventions

Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced; BIOLOGICAL

TAMAVAQ Vaccine plus Poly-ICLC, cGAMP, Granulocyte-macrophage colony stimulating factor (GM-CSF), imiquimod, CpG oligodeoxynucleotides, saponins and monophosphoryl lipid A (MPLA) * TAMAVAQ VACCINE : Each one of our TAMAVAQ VACCINE is consisted of 1-35 (LIMPs, ASPs, and bEPTs) Personalised Synthetic Neoantigenic Peptides mixed with GBM TAAs, including MAGE-1, HER-2, gp100, AIM-2, TRP-2, EphA2,105 survivin50, IL13Rα2, heat-shock peptide protein complex-96 (HSPPC-96), and Smac-TLR7/8 peptides. * TAMAVAQ vaccine products are composed of 1-35 peptides from the Biogenea Pharmaceuticals Ltd warehouse. * TAMAVAQ vaccine will be applied before maintenance TMZ cycles after completion of chemoradiation therapy (CRT). Beginning on day 14 before the first maintenance TMZ cycle, patients will receive 7 vaccinations with TAMAVAC VACCINE

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

Eligibility Criteria

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

You may qualify if:

• \. \*\*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; 2. \*\*Diagnosis\*\*:
• Histologically confirmed diagnosis of glioma, including:
• Glioblastoma multiforme (GBM, WHO grade IV)
• Anaplastic astrocytoma (WHO grade III)

You may not qualify if:

• Patients who have received prior treatment with immune checkpoint inhibitors, other cancer vaccines, or experimental immunotherapies that may interfere with the study outcomes.
• \. \*\*Active Autoimmune Diseases\*\*:
• Patients with active autoimmune diseases or chronic inflammatory conditions requiring systemic treatment (e.g., rheumatoid arthritis, lupus, multiple sclerosis).
• \. \*\*Pregnancy or Breastfeeding\*\*:
• Pregnant or breastfeeding women, as the effects of the vaccine on fetal development or breastfeeding infants are not yet established.
• \. \*\*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.
• \. \*\*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.
• \. \*\*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.
• \. \*\*Severe Allergies\*\*:

Sponsors & Collaborators

• Biogenea Pharmaceuticals Ltd.: lead
• Naval Hospital, Athens: collaborator

Study Sites (1)

Biogenea Pharmaceuticals Ltd

Thessaloniki, 54627, Greece

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Ioannis G Grigoriadis, Pharmacist

  Myoncotherapy

  STUDY DIRECTOR

Central Study Contacts

IOANNIS G GRIGORIADIS, Pharmacist

CONTACT

+306936592686; biogeneadrug@gmail.com

Nikolaos G Grigoriadis, Pharmacist Phd

CONTACT

+306949737710; ngrigoriadis@biogenea.gr

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study intervention for this AI-QMMM designed and glioma treated personalized neoantigenic vaccine clinical trial involves the administration of a customized vaccine designed to elicit a targeted immune response against specific neoantigens present in the participant's tumor. The TAMAVAQ's intervention aims to enhance the body's immune response to glioma cells, potentially improving clinical outcomes in patients with this challenging form of brain cancer. Collectively, our findings are going to suggest that TAMAVAQ can stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. By combining personalized neoantigen identification with a robust vaccine platform and thorough immune monitoring, the TAMAVAQ trial aims to provide valuable insights into the safety and efficacy of this innovative treatment strategy in glioma patients.

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: July 22, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)