GYNORYLAQ™-VLINIVAL™: Ψ-Guided Personalized Neoantigen Peptide Vaccine for High-Risk Endometrial Cancer

NCT07316361 | Enrolling By Invitation Early Phase 1 DMC

• 2 other identifiers: BiogeneaTMMyVaccine4MyVaccine4GYNORYLAQ™
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

GYNORYLAQ-VLINIVAL is an Early Phase I, non-randomized, single-arm, open-label clinical trial enrolling 40 patients with high-risk or recurrent endometrial carcinoma. All participants receive GYNORYLAQ-TM, a personalized neoantigenic peptide vaccine generated by the GYNORYLAQ-EC™ quantum-classical engine, in combination with systemic and supportive drug regimens that are individually selected and prescribed by the treating medical oncologist, Dr Emmanouelides Christos, according to contemporary standards of care and the clinical status of each patient. Only the GYNORYLAQ-TM vaccine is considered investigational within this protocol; all concomitant drugs (including antineoplastic agents and supportive care medications) are non-investigational, chosen and adjusted at the discretion of Dr Emmanouelides Christos. The primary objectives are to evaluate the safety/tolerability of GYNORYLAQ-TM in this real-world therapeutic context and the feasibility of quantum-guided, GMP-grade personalized vaccine manufacture. Secondary and exploratory objectives characterize vaccine-induced T-cell immunity and explore correlations between quantum/physics-based scores and clinical/immunologic outcomes.

Conditions

Endometrial Carcinoma; Endometrial Carcinoma Stage III

Keywords

Endometrial carcinoma; Personalized neoantigen vaccine; Peptide-based cancer immunotherapy; Quantum-classical vaccine design (GYNOLYVAQ-EC™); Tumour-specific neoantigens; Immunogenicity and T-cell responses; Early phase I interventional clinical trial

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent AEs/SAEs and DLTs (CTCAE v5.0) With GYNORYLAQ™ Plus Oncologist-Selected Drug Regimens

  Incidence, severity (CTCAE v5.0 grade), type, and attribution of treatment-emergent adverse events (AEs) and serious adverse events (SAEs), and identification of dose-limiting toxicities (DLTs) during the defined DLT window, accounting for concomitant therapies prescribed by Dr. Christos Emmanouelides.

  From first vaccination through 30 days after last vaccination.

• Feasibility of Quantum-Guided Vaccine Manufacturing

  Proportion of participants for whom: adequate tumour and matched normal samples are obtained, the GYNORYLAQ-EC™ pipeline completes successfully, a minimum number of peptides (e.g., ≥10) are synthesized and pass QC, and first vaccination occurs within a prespecified time limit (e.g., ≤16 weeks).

  Up to 16 weeks from tumor tissue acquisition to vaccine release and first vaccination.

• Vaccine Immunogenicity (Early Phase I Co-Primary)

  Proportion of patients with de novo or boosted T-cell responses to ≥1 vaccine peptide (ELISpot/ICS), and quantitative change in vaccine-specific T-cell frequencies, in the context of concomitant oncologist-managed therapy.

  Baseline to ~Week 24 and at end of treatment.

Secondary Outcomes (6)

• Number of distinct GYNORYLAQ vaccine peptides recognized by participant T cells

  Baseline; selected on-treatment timepoints; follow-up to ~12 months.

• Number of participants with persistent vaccine-induced peptide-specific immune responses (≥3-fold increase)

  Up to ~12 months after first vaccination.

• Objective Response Rate (ORR) in participants with measurable disease receiving GYNORYLAQ-TM plus oncologist-selected therapy

  Up to ~36 months.

• Correlation of quantum/physics-based peptide metrics and predicted immunogenicity probabilities with observed immune and clinical outcomes

  Baseline through study completion (an average of 3 years).

• Number and proportion of participants with protocol-defined dose-limiting toxicities (DLTs) related to GYNORYLAQ-TM

  From first vaccination through the end of the DLT evaluation window (up to 84 days; Cycles 1-3, each cycle is 28 days).

Other Outcomes (21)

• Dose-Limiting Toxicities (DLTs) and Early Safety Signal Detection

  From first vaccination through the predefined DLT window (e.g., first 2-3 vaccination cycles).

• Vaccine immunogenicity responder rate (T-cell response to ≥1 GYNORYLAQ-TM peptide)

  Baseline to approximately Week 24 and end of treatment (approximately Week 24).

• Treatment Deliverability: Completion of Planned Priming Vaccinations

  : From first vaccination to completion of the planned priming phase (e.g., Weeks 0-8).

Study Arms (1)

GYNORYLAQ-TM Vaccine With Concomitant Oncologist-Selected Drug Therapy

EXPERIMENTAL

All participants receive: * GYNORYLAQ-TM personalized neoantigenic peptide vaccine according to the Early Phase I vaccination schedule, and * Concomitant systemic and supportive drug regimens selected and prescribed by Dr Emmanouelides Christos, based on tumour characteristics, prior treatments, tolerability, and standard-of-care guidelines. Only GYNORYLAQ-TM is investigational; all concomitant medications are standard practice and non-investigational.

Biological: • Biological: GYNORYLAQ-TM Personalized Neoantigenic Peptide Vaccine

Interventions

• Biological: GYNORYLAQ-TM Personalized Neoantigenic Peptide Vaccine BIOLOGICAL

GYNORYLAQ-TM is an individualized, peptide-based cancer vaccine composed of synthetic neoantigenic peptides uniquely selected for each patient using the GYNORYLAQ-EC™ quantum-classical computational engine. Tumour and matched normal samples are sequenced to identify somatic variants (missense mutations, indels, frameshifts). For each patient, candidate peptide-HLA pairs are generated and scored using an integrated feature set that includes sequence-based presentation predictions, antigen-processing priors, quantum-geometric similarity measures, structural pocket occupancy, and docking-derived thermodynamic parameters (ΔG°, K\_d). Peptides passing predefined gates on binding strength, quantum similarity, and predicted immunogenicity are prioritized to form a personalized panel (typically \~10-20 peptides, including 8-11mer class I and longer helper/cross-presenting peptides) suitable for GMP synthesis.

GYNORYLAQ-TM Vaccine With Concomitant Oncologist-Selected Drug Therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent and Legal Capacity 1.1. Ability to understand the nature of the study and provide written informed consent personally or via a legally authorized representative, in accordance with local regulations.
• Willingness and ability (participant and/or guardian) to comply with scheduled visits, vaccination procedures, blood draws, imaging, and other study-related assessments.
• Diagnosis and Histology 2.1. Histologically confirmed endometrial carcinoma (endometrioid, serous, clear cell, mixed histology, carcinosarcoma, or other specified high-risk subtypes), documented by pathology report.
• High-risk, recurrent, or metastatic disease, defined by at least one of: FIGO Stage III or IV at initial diagnosis, and/or Recurrent or progressive disease after prior surgery ± radiotherapy ± systemic therapy, not amenable to curative-intent surgery or radiotherapy.
• Disease Status at Enrollment 3.1. Radiologically measurable disease per RECIST v1.1, or evaluable disease if allowed by protocol (e.g., measurable by other validated imaging or biomarker criteria).
• Disease status documented by CT/MRI (or PET/CT, if local standard) within 28 days before the first GYNORYLAQ-TM vaccination.
• Prior Anti-cancer Therapy 4.1. Participants may have received prior surgery, radiotherapy, chemotherapy, endocrine therapy, and/or targeted agents, provided all of the following apply:
• weeks since last dose of cytotoxic chemotherapy (≥6 weeks for mitomycin C or nitrosoureas).
• weeks since last dose of endocrine therapy (if applicable).
• weeks (or 5 half-lives, whichever is longer) since last dose of any investigational systemic agent or biologic therapy.
• weeks since completion of palliative radiotherapy to non-CNS sites, with radiotherapy-related toxicities recovered to Grade ≤1 (CTCAE v5.0).
• Recovery from acute toxicity of prior therapies to Grade ≤1 or baseline (CTCAE v5.0), except for: Alopecia, Stable peripheral neuropathy (≤Grade 2), Other protocol-specified exceptions. 4.3. Prior immune checkpoint inhibitor therapy (e.g., anti-PD-1/PD-L1) is allowed, provided there is no history of Grade ≥3 immune-related adverse event that mandated permanent discontinuation.
• Suitability for Systemic Therapy (Clinical Practice Integration) 5.1. In the opinion of the treating medical oncologist Dr Emmanouelides Christos, the participant is suitable for ongoing systemic anti-cancer and supportive drug treatment (e.g., chemotherapy, endocrine therapy, targeted therapy) consistent with prevailing guidelines and local standards of care.
• There is no absolute contraindication to all forms of systemic therapy that might reasonably be selected by Dr Emmanouelides Christos.
• The participant agrees that systemic and supportive drugs will be chosen, initiated, and adjusted by Dr Emmanouelides Christos and recorded as background therapy.

You may not qualify if:

• Tumour and Disease Characteristics 1.1. Cancers not consistent with endometrial carcinoma as primary site (e.g., primary cervical or ovarian carcinoma) unless clearly documented as metastatic/endometrial in origin.
• Disease requiring urgent, life-saving intervention that would preclude safe vaccine administration (e.g., impending organ failure requiring immediate surgery or high-dose radiotherapy).
• Disease burden or rate of progression such that, in the opinion of the investigator and/or Dr Emmanouelides Christos, any delay associated with vaccine manufacturing and initiation of protocol therapy would be unsafe.
• Prior Therapies and Confounding Investigational Products 2.1. Prior receipt of neoantigen-specific or tumour vaccine products that target highly overlapping epitope sets in a way that would confound interpretation of GYNORYLAQ-TM-induced responses, unless approved case-by-case.
• Participation in another interventional clinical trial with therapeutic intent or receipt of an investigational systemic agent within 4 weeks (or 5 half-lives, whichever is longer) before first GYNORYLAQ-TM dose, unless discussed with and approved by the sponsor/investigator.
• Prior allogeneic hematopoietic stem cell or solid organ transplantation. Autoimmune and Immune-mediated Conditions 3.1. Active, known, or suspected autoimmune disease requiring systemic immunosuppressive treatment (e.g., ≥10 mg/day prednisone equivalent) within the past 12 months, including but not limited to: Systemic lupus erythematosus Inflammatory bowel disease (Crohn's disease, ulcerative colitis) Multiple sclerosis Severe rheumatoid arthritis, systemic sclerosis, vasculitis Autoimmune hepatitis 3.2. Acceptable exceptions may include: Controlled autoimmune thyroiditis on stable hormone replacement Vitiligo, type 1 diabetes mellitus, or psoriasis not requiring systemic immunosuppression Other minor or stable autoimmune conditions deemed acceptable by the investigator.
• Concomitant Immunosuppressive Therapy 4.1. Chronic systemic immunosuppressive therapy including: Steroid therapy equivalent to \>10 mg/day prednisone for more than 14 consecutive days within 30 days prior to first vaccine dose, or Other immunosuppressive agents (e.g., calcineurin inhibitors, mTOR inhibitors, anti-TNF agents) without a washout period acceptable to the investigator.
• Short-term steroid use (e.g., antiemetic prophylaxis, contrast premedication, acute reaction management) is permitted as long as it is not chronic.
• Central Nervous System Disease 5.1. Untreated or unstable CNS metastases or carcinomatous meningitis. 5.2. Participants with previously treated CNS metastases may be eligible if all of the following are true: Radiologically stable or responding for ≥4 weeks after completion of CNS-directed therapy, and Neurologically stable, and Off systemic corticosteroids (or on physiologic replacement doses only) for ≥2 weeks prior to first vaccine dose.
• Cardiovascular, Pulmonary, and Other Serious Comorbidities 6.1. Clinically significant, uncontrolled cardiovascular disease, including: Myocardial infarction within 6 months, Unstable angina, Significant uncontrolled arrhythmias (excluding controlled atrial fibrillation), Symptomatic congestive heart failure (NYHA Class III-IV), Uncontrolled hypertension (e.g., systolic ≥180 mmHg or diastolic ≥100 mmHg despite treatment).
• History of venous thromboembolism (DVT/PE) that is not adequately anticoagulated, or acute events within 4 weeks prior to screening that pose high risk in the investigator's judgment.
• Severe, uncontrolled pulmonary disease, such as advanced COPD, interstitial lung disease with active symptoms, or chronic oxygen dependence that would substantially increase risk.
• Active Infections 7.1. Active, uncontrolled bacterial, viral, or fungal infection requiring IV therapy or hospitalization.
• Other Malignancies 8.1. Another active malignancy within the past 3 years, excluding: Curatively treated non-melanoma skin cancers, In situ carcinoma (e.g., cervical, breast, bladder) treated with curative intent, Other malignancies considered by the investigator to have negligible risk of recurrence and unlikely to interfere with study participation or interpretation.
• Hypersensitivity 9.1. Known severe hypersensitivity or anaphylaxis to any component of the GYNORYLAQ-TM peptide vaccine or its excipients.

Sponsors & Collaborators

• Biogenea Pharmaceuticals Ltd.: lead

Study Sites (1)

Biogenea Pharmaceuticals Ltd & Interbalkan Medical Center - International Oncology Center

Thessaloniki, Thessaloniki, 54622, Greece

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

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

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: January 5, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): December 2, 2029
• Study Completion (Estimated): December 2, 2031
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)