AI-designed TAMAVAQ personalized vaccine for 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.

This will test an AI-designed personalized peptide vaccine (TAMAVAQ) in adults with newly diagnosed glioma to see if it is safe and triggers an immune response against each patient's tumor.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Biogenea Pharmaceuticals Ltd. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Thessaloniki)
• Trial ID: NCT07077616 on ClinicalTrials.gov

What this trial studies

This early Phase 1 interventional protocol creates a personalized neoantigen peptide vaccine using each patient's tumor and blood sequencing. Whole-exome and RNA sequencing of tumor tissue and PBMC DNA are used to identify coding mutations, determine HLA type, and predict candidate neoantigen peptides with predicted MHC binding (IC50 < 500 nM). AI, machine learning, and quantum-circuit algorithms prioritize immunodominant neo-epitopes, which are synthesized as peptides and administered to participants while monitoring safety and immune responses. The primary focus is safety with exploratory measures of immune activation and early signs of therapeutic activity in patients meeting tissue and mutation-burden requirements.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed glioma (including GBM) who can provide tumor tissue and blood, have at least one measurable lesion, adequate organ and bone marrow function, KPS > 60, and a high tumor mutational burden (≥10 TMB) are the intended participants.

Not a fit: Patients with low tumor mutation burden, inability to provide adequate tumor tissue or blood samples, prior immunotherapy, very poor performance status, or very limited life expectancy are unlikely to benefit from this personalized vaccine approach.

Why it matters

Potential benefit: If successful, the vaccine could train each patient's immune system to recognize and attack tumor-specific neoantigens, potentially slowing disease progression and improving survival.

How similar studies have performed: Neoantigen vaccines have elicited immune responses and occasional clinical signals in early trials for other cancers and small glioma studies, but they remain experimental and are not yet proven or FDA-approved for glioblastoma.

Eligibility criteria

Inclusion Criteria:

* 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; 2. \*\*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.

Exclusion Criteria: 1. \*\*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. -

Where this trial is running

Thessaloniki

• Biogenea Pharmaceuticals Ltd — Thessaloniki, Greece (RECRUITING)

Study contacts

• Study coordinator: IOANNIS G GRIGORIADIS, Pharmacist

Conditions: Glioma, Personalised Vaccine, Neoantigenic Peptides, AI-designed, Machine Learning-predicted, Quantum Mechanics structured, Molecular Dynamics-modeled, Immunodominant Peptides