NCT07077616

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

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.

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Biogenea Pharmaceuticals Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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. Potential for Long-term Remission\*\*:- By training the immune system to identify and remember glioma cells, patients may achieve longer-lasting remission rates and a reduced likelihood of tumor recurrence compared to conventional therapies.\*\*Reduction in Side Effects\*\*:- Compared to traditional treatments such as chemotherapy and radiation, which often come with significant side effects, the TAMAVAQ personalized neoantigen vaccine may result in fewer adverse effects, thereby improving the patient's quality of life. Personalized Treatment Approach\*\*:- Each TAMAVAQ vaccine is tailored to the individual patient's tumor profile, potentially increasing the efficacy of the treatment. This personalization allows for a more precise approach to therapy that aligns with the unique characteristics of each Glioma patient's cancer. Opportunities for Combination Therapies\*\*:- The TAMAVAQ vaccine can potentially be used in conjunction with other treatments (e.g., checkpoint inhibitors, targeted therapies), enhancing overall treatment effectiveness and providing a multifaceted approach to combat glioma.\*\*Real-time Monitoring and Adaptation\*\*:- This clinical trial setting allows for continuous monitoring of patient responses, providing valuable data that can lead to adaptations in treatment strategies based on observed efficacy and safety profiles. Contribution to Scientific Knowledge\*\*:- The TAMAVAQ trial can provide critical insights into the mechanisms of immune responses against gliomas, contributing to the broader understanding of cancer immunotherapy and paving the way for future treatments.\*\*Potential for Broader Application\*\*:Success in the glioma trial may lead to the development of similar personalized vaccines for other cancer types, expanding the impact of this innovative therapeutic approach.\*\*Patient Empowerment and Engagement\*\*:Participation in TAMAVAQ clinical trials often empowers patients by involving them in cutting-edge research, providing them with access to novel therapies and fostering a sense of hope in their treatment journey. This TAMAVAQ clinical trial holds substantial potential benefits, ranging from enhanced targeted therapy and immune activation to improved patient quality of life and contributions to scientific knowledge. As research progresses, it is essential to continue evaluating these benefits in conjunction with the associated risks to optimize treatment strategies for glioma patients.The development of the TAMAVAQ personalized vaccine represents a novel approach to glioma treatment. This analysis evaluates the potential risks and benefits associated with conducting a clinical trial for this innovative therapeutic strategy. This clinical trial aims to assess the safety, tolerability, and efficacy of a personalized neoantigenic vaccine designed for patients diagnosed with glioma. The TAMAVAQ study will involve identifying patient-specific neoantigens from tumor biopsies and formulating tailored vaccines to stimulate an immune response against glioma cells. Following surgery, patients will receive conventional radiation therapy administered at 180-200 cGy per fraction daily for five days per week to a total of approximately 60 Gy. Personalized neoantigen vaccines TAMAVAQ NeoVaccine will be prepared using information from fresh tumour and normal tissue obtained at the time of diagnostic resection, as described below. Algorithms and methods based on profiles of sequence motifs, quantitative matrices (QM), artificial neural networks (ANN), support vector machines (SVM), quantitative structure activity relationship (QSAR), T-cell major histocompatibility complex (MHC) class I binding prediction and molecular docking simulations among others will be combined and used in order to predict and design the TAMAVAQ NeoVaccine-Drug Product Neo-epitopes. Quantum chemical calculations (IBM Quantum Studio) will be used to predict the TAMAVAQ NeoVaccine-Drug Product's biological function and be applied to T-cell receptor interaction with TAMAVAQ NeoVaccine-Drug Product Peptide/MHC class I. A cluster of algorithms is proposed here using semi-empirical quantum mechanical methods for calculating peptide-MHC class I and II molecules binding energy for the rational design of T-cell TAMAVAQ NeoVaccine-Drug Product Neo-epitopes with application in cancer glioma vaccinology. The vaccine will be administered subcutaneously at least seven to twelve weeks following completion of external beam radiotherapy. TAMAVAQ NeoVaccine-Drug Product will be applied before maintenance of TMZ cycles after completion of chemoradiation therapy (CRT). Beginning on day 14 before the first maintenance TMZ cycle, patients will receive 7 vaccinations with TAMAVAQ NeoVaccine drug products during 7 weeks. 20-200 μg per peptide per vial are used followed by two booster doses eight and sixteen weeks later. For each dose, vaccine will be administered within six hours of thawing in a non-rotating fashion to one of up to four extremities. Patients will be repeatedly vaccinated with TAMAVAQ NeoVaccine drug products beginning on day 33 of the 6 maintenance TMZ cycle. Patients will receive 9 vaccinations within 12 weeks. 20-400 μg per peptide per vial will be used. Concomitant medications deemed necessary for adequate patient care will be allowed, including concomitant corticosteroids for symptoms associated with cerebral oedema, but the study vaccine will be held for patients requiring more than 4 mg per day of dexamethasone within seven days of vaccine administration. Clinical assessment and monitoring will be delivered by using the RANO criteria and the Immunotherapy Response Assessment in the Neuro-Oncology criteria. Study Design * Type\*\*: Open-label, single-arm, multicenter clinical trial * Phase\*\*: Phases I \& II * Duration\*\*: Approximately 24 months (including recruitment, treatment, and follow-up) Methodology Screening Phase (Month 1-2)\*\*: Recruitment\*\*: Patients will be recruited from participating medical centers and clinics. Informed Consent\*\*: Obtain informed consent from eligible patients. Screening Assessments\*\*: Conduct baseline assessments, including medical history, imaging, and laboratory tests to confirm eligibility. Vaccine Development Phase (Month 3-5)\*\*: Tumor Biopsy\*\*: Collect tumor samples from enrolled patients for sequencing and neoantigen identification. Neoantigen Identification\*\*: Utilize computational algorithms and laboratory techniques to identify patient-specific neoantigens. Vaccine Formulation\*\*: Develop personalized vaccines based on identified neoantigens tailored to each patient. Vaccination Phase (Month 6)\*\*: -\*\*Pre-Vaccination Assessments\*\*: Conduct baseline assessments, including physical examinations and laboratory tests before vaccine administration. * TAMAVAQ Vaccine Administration\*\*: Administer the TAMAVAQ personalized neoantigenic vaccine via subcutaneous or intradermal injection. * Immediate Post-Vaccination Monitoring\*\*: Monitor patients for immediate side effects and adverse reactions for a specified period following vaccination. Follow-Up Phase (Month 7-24)\*\*: Regular Follow-Up Visits\*\*: Schedule follow-up visits at regular intervals (e.g., every 4-6 weeks) to assess patient health, side effects, and immune response. Adverse Event Monitoring\*\*: Continuously monitor and report any adverse events or serious adverse events to regulatory authorities.\*\*Imaging and Laboratory Assessments\*\*: Conduct imaging studies (e.g., MRI) and laboratory tests to evaluate treatment response and tumor status at designated follow-up intervals. Quality of Life Assessments\*\*: Administer validated quality of life questionnaires at baseline and follow-up visits to assess the impact of AI-QMMM designed TAMAVAQ treatment.\*\*Study Closure (Month 24)\*\*: Final Patient Assessments\*\*: Conduct final assessments for all participants to evaluate long-term outcomes and safety. Data Analysis and Reporting\*\*: Analyze TAMAVAQ trial data and prepare reports for submission to regulatory authorities and publication in scientific journals. Feedback and Follow-Up\*\*: Provide TAMAVAQ vaccinated participants with feedback on trial outcomes and offer continued follow-up care or access to alternative treatments as needed. Sample Size - Estimated based on expected effect size and power calculations, aiming for a target enrollment of approximately 50-140 patients to provide adequate statistical power for the primary and secondary endpoints. Statistical Analysis Descriptive Statistics\*\*: To summarize demographic and baseline characteristics. Efficacy Analysis\*\*: Kaplan-Meier survival curves for progression-free survival (PFS) and overall survival (OS). Adverse Events Analysis\*\*: Frequency and severity of adverse events reported according to NCI CTCAE criteria.

Conditions

• Glioma

Interventions

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

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-12-01
• Completion: 2029-12-01
• First posted: 2025-07-22
• Last updated: 2025-12-08

Locations

1 site across 1 country: Greece