NSCLC (Non-small Cell Lung Cancer)Early Phase 1Microlyvaq™NCT07285434
Clinical Study of the Therapeutic Effectiveness of In-silico-Designed, Machine Learning Inspired, and Quantum-molecularly Coupled Personalized Neoantigenic Vaccines Microlyvaq™ in Patients With Advanced Non-small Cell Lung Cancer
A Early Phase 1 study testing Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) in people with NSCLC (Non-small Cell Lung Cancer) and Squamous Lung Cancer With FGFR1 Amplification, run by Biogenea Pharmaceuticals Ltd. at 1 site in Greece.
Trial summary
Microlyvaq™ is a first-line, non-randomized, two-arm clinical trial in advanced non-small cell lung cancer (NSCLC). In both arms, patients receive a personalized multi-epitope vaccine (Microlyvaq™) on top of standard-of-care chemo-immunotherapy, with treatment tailored by histology: Arm 1 - Squamous NSCLC: Microlyvaq™… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- NSCLC (Non-small Cell Lung Cancer), Squamous Lung Cancer With FGFR1 Amplification, Non-Squamous Non Small Cell Lung Cancer
- What is being tested?
- Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteGreece
- Study dates
- 2 Feb 2026to 2 Feb 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- -
- Subjects are eligible if all of the following are met:
- Age
- ≥18 years at the time of informed consent. Diagnosis / Histology
- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is:
- Non-squamous (e.g. adenocarcinoma, large-cell, NSCLC-NOS adjudicated non-squamous), or Squamous (if/when that stratum is open). Diagnosis must be locally documented and source-verifiable. Stage / Disease Status Stage IIIB / IIIC / IV or recurrent/metastatic NSCLC not amenable to curative surgery or radiotherapy, per AJCC 8th edition staging.
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- Disease is considered first-line metastatic/systemic setting:
- No prior systemic therapy for advanced/metastatic disease in this line. Prior adjuvant/neoadjuvant therapy or consolidation chemo-RT is allowed if completed and the subject relapsed outside the protocol-defined disease-free interval (e.g. relapse ≥6-12 months after completion, per final protocol text).
- Measurable Disease At least one measurable lesion per RECIST v1.1 at baseline imaging. Baseline imaging must be within 28 days prior to Day 1 (CT chest/abdomen/pelvis ± contrast, plus brain MRI if clinically indicated).
- ECOG Performance Status ECOG 0 or 1 at screening. Subject must be ambulatory and clinically stable enough to receive combination therapy (pembrolizumab + chemo ± Microlyvaq™).
- Adequate Organ and Marrow Function (Representative thresholds - to be finalized numerically in the protocol SOP, but typically:) Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L. Platelets ≥100 × 10⁹/L. Hemoglobin ≥9.0 g/dL (transfusion allowed per institutional standard prior to enrollment).
- AST and ALT ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN if liver metastases are present.
- Total bilirubin ≤1.5 × ULN (≤3 × ULN if known Gilbert's syndrome). Creatinine clearance / eGFR ≥45 mL/min/1.73 m² (sufficient for pemetrexed/platinum; final numeric cutoff may align to pemetrexed label).
- Coagulation: INR and aPTT compatible with safe biopsy (if biopsy expected) per site policy.
- Oxygenation: No resting hypoxemia prohibitive for safe treatment in investigator judgment.
- Tumor Tissue Availability
- Adequate tumor material must be available for:
- PD-L1 assessment, DNA/RNA extraction (whole exome sequencing / RNA-seq or targeted panel sufficient for epitope discovery), High-resolution HLA typing support, Optional spatial profiling.
- Acceptable sources:
- Recent core needle biopsy or surgical specimen (preferred), OR Archival FFPE block or ≥15 unstained slides with documented tumor cellularity. Tumor cellularity must meet the minimum input requirement for sequencing and PD-L1 scoring (macrodissection allowed).
- Biospecimen / Translational Willingness
- Willing and able to provide required blood samples at protocol-defined timepoints:
- PBMC (for ELISpot, ICS, TCR sequencing), Plasma/serum (for ctDNA, exosomal miRNA, cytokines), HLA typing. Willing to allow shipment of these biospecimens under chain-of-custody to central labs.
- Willing to undergo optional on-treatment biopsy (e.g. around Cycle 3 / ~Week 6-9) if, in the investigator's judgment, it is clinically safe and technically feasible. If unsafe, liquid biopsy alone is acceptable.
- Contraception / Reproductive Status Females of childbearing potential: negative pregnancy test at screening and prior to first dose.
- Females of childbearing potential and males with partners of childbearing potential must agree to use highly effective contraception during study treatment and for the protocol-defined post-treatment window:
- Typically ≥120 days after last pembrolizumab dose and ≥90 days after last Microlyvaq™ dose, whichever is longer (final timing per protocol).
- No intention to conceive or donate gametes during this protection window. Informed Consent
- Capable of understanding and signing informed consent(s), including:
- Main study consent (chemo + pembrolizumab + Microlyvaq™), Genomic profiling / HLA typing consent, Optional on-treatment biopsy / leukapheresis consent (if applicable at site), Data/privacy language (GDPR-compliant). Willing to comply with study visits, dosing schedule, safety monitoring, PRO questionnaires (if enrolled in PRO subset), and survival follow-up.
Who cannot join
- Subjects must not meet any of the following:
- Prior Systemic Therapy in Metastatic Setting Any prior systemic therapy for metastatic / unresectable NSCLC in the current line.
- Exception: prior adjuvant/neoadjuvant chemo, IO, or chemoradiation allowed if relapse occurred outside the protocol's defined exclusion interval (e.g. relapse ≥6-12 months after completion); exact interval to be specified.
- Known Oncogene-Addicted Disease Requiring Targeted SOC Subjects whose tumors harbor actionable drivers for which an approved targeted therapy is standard first-line care (e.g. EGFR activating mutation, ALK rearrangement, ROS1 rearrangement, certain ERBB2/HER2 drivers, MET exon 14 skipping, RET fusion, NTRK fusion, KRAS G12C where local standard is targeted frontline) may be excluded or enrolled only in specific sub-cohorts if allowed by the statistical design.
- Rationale: It may be unethical to withhold proven first-line targeted agents. The final protocol will define whether these genotypes are (a) excluded, (b) stratified, or (c) routed to a molecularly restricted exploratory cohort.
- Uncontrolled CNS Disease Active, symptomatic brain metastases or leptomeningeal disease requiring immediate local intervention.
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- Allowed:
- Previously treated/stable brain metastases are permitted if:
- Clinically stable, Off high-dose steroids (e.g. >10 mg prednisone equivalent daily) for ≥14 days before Day 1, No new/worsening neurologic symptoms for ≥2 weeks.
- Excluded:
- Ongoing steroid dependency above immunosuppressive thresholds, uncontrolled seizures, mass effect with high intracranial pressure, or unstable neuro deficits judged unsafe.
- Autoimmune / Immune-Mediated Conditions of Concern Active, uncontrolled autoimmune disease that has required systemic immunosuppression >10 mg/day prednisone-equivalent (or biologic immunosuppressive agent) within 14 days prior to Day 1.
- History of severe (life-threatening) immune-related adverse event (irAE) to prior PD-1/PD-L1/CTLA-4 (e.g. Grade 4 pneumonitis, myocarditis, neurologic irAE that did not fully resolve), unless cleared by Medical Monitor.
- Autoimmune disorders that are mild, stable, and not expected to flare under PD-1 blockade (e.g. controlled hypothyroidism on replacement; vitiligo; stable type 1 diabetes on insulin) may be allowed.
- Significant Active Infection Any uncontrolled active infection requiring IV antibiotics or hospitalization at screening.
- Uncontrolled HBV, HCV, or HIV viremia above protocol thresholds:
- HBV: high viral load without appropriate antiviral management. HCV: untreated, high-level viremia with ongoing hepatic decompensation. HIV: uncontrolled (e.g. not on stable antiretroviral therapy, CD4 below a prespecified safe cutoff); final numeric cutoffs defined in protocol.
- Active tuberculosis or other serious opportunistic infection. Clinically Significant Pulmonary Compromise Baseline pneumonitis requiring steroids. Prior ≥Grade 3 immune-mediated pneumonitis from checkpoint inhibitor therapy that did not resolve to ≤Grade 1.
- Severe, uncontrolled interstitial lung disease that would make pembrolizumab plus investigational immunostimulation unsafe.
- Other Serious Uncontrolled Comorbidities Uncontrolled congestive heart failure, unstable angina, recent myocardial infarction or stroke (typically <6 months).
- Clinically significant uncontrolled arrhythmia. Severe uncontrolled hypertension. Any condition that, in the investigator's judgment, would make study therapy unacceptably high risk (e.g. ECOG drift, frailty, severe malnutrition).
- Bleeding Risk / Biopsy Unsuitability (When Biopsy is Expected) Active, clinically significant bleeding or coagulopathy that cannot be corrected.
- Platelet count or anticoagulation status that, in investigator judgment, makes mandatory biopsy unsafe.
- NOTE: If a site/arm requires an on-treatment biopsy for core analysis and it is deemed unsafe, subject may still be eligible if protocol allows liquid-biopsy-only participation in that stratum. (This must be explicitly permitted to avoid excluding medically fragile patients.) Known Hypersensitivity Known severe hypersensitivity (e.g. anaphylaxis) to pembrolizumab, to the planned chemotherapy backbone (e.g. pemetrexed, carboplatin) despite standard premedication strategies, or to critical Microlyvaq™ excipients / adjuvant components.
- In pemetrexed-containing regimens: inability/unwillingness to receive mandatory folate and vitamin B12 supplementation and steroid premedication.
- In carboplatin regimens: uncontrolled prior carboplatin hypersensitivity not manageable by desensitization.
- Pregnancy / Breastfeeding Pregnant or breastfeeding at screening. Intention to become pregnant (or impregnate a partner) during study therapy or within the required contraception window after last dose.
- Concurrent Participation in Confounding Interventional Trials Enrollment in another interventional clinical study that could confound efficacy/safety readouts or interfere with immune profiling.
- Exceptions:
- Non-interventional / observational registries, Certain supportive care trials with Medical Monitor approval, Protocol-approved combination substudies (if integrated under the Microlyvaq™ umbrella and statistically planned).
- Any Condition That Interferes With Protocol Compliance
- Inability or unwillingness to comply with:
- Scheduled visits, Biospecimen collections (for HLA typing, PBMC isolation, ctDNA, etc.), Imaging schedule (q6 weeks through Week 24, then q9-12 weeks), Safety follow-up and PRO questionnaires (if PRO subset), Survival follow-up calls ~q12 weeks post-treatment. Cognitive, psychiatric, or social situations that in the investigator's judgment would preclude safe, reliable participation and follow-up.
- Notes / Operational Clarifiers
- HLA typing and sequencing feasibility:
- The subject must have enough viable tumor + PBMC DNA/RNA to allow:
- WES / RNA-seq or equivalent targeted sequencing for neoantigen discovery, High-resolution HLA-A/B/C typing. If a subject cannot generate a viable personalized epitope set (e.g. insufficient material for immunogen design), that subject may be ineligible for Microlyvaq™ dosing but could be eligible for safety follow-up / SOC reference cohorts, depending on how the arm is structured.
- Brain metastases:
- Stable, treated, asymptomatic brain mets are allowed. This matters in first-line metastatic NSCLC, because excluding all brain mets would make the trial clinically irrelevant. The key exclusion is uncontrolled CNS disease requiring urgent steroids/radiation/surgery.
- Actionable oncogene drivers:
- Final protocol must say explicitly whether EGFR/ALK/ROS1/etc. are:
- excluded entirely, allowed but stratified, or diverted to exploratory "post-standard-targeted-therapy" cohorts. This is both ethical and regulatory: you don't want to randomize someone away from globally recognized, mutation-directed SOC.
- Autoimmune disease:
- The bar is not "no autoimmune history ever." It's "no uncontrolled, high-risk autoimmune activity that would likely flare catastrophically when we give a personalized Th1-skewing vaccine + PD-1 blockade."
- Contraception window:
- Needs to line up with pembrolizumab label and with any reproductive toxicity data from Microlyvaq™ (e.g. ≥120 days / ≥90 days windows). Keep that harmonized across patient materials, pharmacy manual, and consent.
- This criteria block is inspection-facing: it protects safety, preserves interpretability of immune endpoints, ensures we can actually manufacture/deliver a personalized Microlyvaq™ lot, and keeps the population consistent with first-line pembrolizumab+chemo standards in advanced NSCLC.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Microlyvaq™ is a first-line, non-randomized, two-arm clinical trial in advanced non-small cell lung cancer (NSCLC). In both arms, patients receive a personalized multi-epitope vaccine (Microlyvaq™) on top of standard-of-care chemo-immunotherapy, with treatment tailored by histology:
Arm 1 - Squamous NSCLC: Microlyvaq™ + carboplatin AUC 5 + paclitaxel 175 mg/m² + pembrolizumab Arm 2 - Non-squamous NSCLC: Microlyvaq™ + carboplatin AUC 5 + pemetrexed 500 mg/m² + pembrolizumab Because this is a non-randomized study, patients are assigned to arms based on tumor histology (squamous vs non-squamous), not by random allocation.
Read more
The core problem it addresses is that even with pembrolizumab plus histology-appropriate chemotherapy, many patients either never respond or respond briefly and then progress. Tumors evade by exhausting T cells, excluding them from the tumor bed, evolving antigen loss, and maintaining suppressive myeloid and stromal niches. Microlyvaq™ is designed to overcome these resistance modes by actively installing new, durable, polyfunctional anti-tumor immunity rather than relying only on pre-existing T cells.
Here's how it works. Each patient's tumor is sequenced (whole exome and RNA-seq) to identify both well-known lung cancer-associated antigens (e.g. NY-ESO-1, SOX2, p53, MAGE-A4, BRAF, BMI1, FXR1, HuD, HuC, CAGE) and private neoantigens created by that tumor's specific mutations, fusions, and splice variants. From this large antigen pool, machine learning models score each candidate epitope for that specific patient. The models consider predicted HLA class I and II presentation, how efficiently the antigen will actually be processed and displayed, whether it's expressed in tumor but not healthy tissue, how essential it is to most malignant cells (to avoid easy escape), and whether it is likely to drive functional, non-exhausted T-cell responses. This is not a generic ranking; it is individualized per patient.
The most promising epitopes then undergo a quantum molecular coupling evaluation. Instead of simply asking whether a peptide binds a given HLA, Microlyvaq™ modeling simulates the peptide-MHC complex as a physical system and approximates solutions to Ĥψ = Eψ to estimate whether the peptide will form a stable, low-energy, presentation-competent conformation that a realistic T-cell receptor can dock to without high energetic penalty. Epitopes that look good in simple binding screens but are predicted to be unstable, transient, or geometrically inaccessible to TCRs are excluded. The remaining epitope set is engineered to: (1) recruit potent CD8⁺ cytotoxic T cells that can kill tumor cells, and (2) recruit CD4⁺ Th1 helper T cells that produce IFN-γ, TNF-α, and IL-2 to sustain and support those killers. The vaccine is therefore intentionally multi-epitope, Th1-biased, and patient-specific.
Each personalized Microlyvaq™ lot is manufactured under GMP and given as a prime-boost series in sync with pembrolizumab and the appropriate chemotherapy backbone for the patient's histologic arm (carboplatin/paclitaxel for squamous; carboplatin/pemetrexed for non-squamous). Timing is deliberate: chemotherapy induces immunogenic tumor cell death and antigen release and transiently "opens up" the tumor microenvironment, while pembrolizumab lifts PD-1-mediated brakes on emerging T cells. Microlyvaq™ is dosed into that vulnerable window to expand vaccine-encoded clones just as new antigen is exposed and suppression is partially relieved. The goal is to generate rapid tumor shrinkage, then sustained immune pressure on residual disease, plus epitope spreading - where the immune system begins to recognize additional tumor targets beyond those in the vaccine, making escape more difficult.
The trial itself is structured as a seamless, adaptive, non-randomized Phase I/IIa study, with two predefined histology-based arms (squamous vs non-squamous) rather than randomized treatment allocations. The primary early endpoint is objective response rate (RECIST v1.1). Key secondary endpoints include progression-free survival, duration of response, and overall survival. In addition, the study incorporates real-time translational signals as decision points, including:
- polyfunctional Th1 and CD8⁺ responses to vaccine epitopes by ELISpot/ICS,
- durable expansion and persistence of vaccine-linked TCR clonotypes in blood and, when feasible, in tumor,
- rapid decline in circulating tumor DNA as an early molecular marker of tumor clearance,
- improved tumor infiltration by CD8⁺ and Th1 cells, and
- remodeling of the tumor microenvironment away from suppressive myeloid states. If a given histology arm shows strong clinical responses plus these immune/molecular signals, that arm can seamlessly expand into survival-powered confirmation. If it does not, predefined futility rules allow that arm to stop, all within this non-randomized, adaptive framework.
Read the detailed description
This is an early Phase I, non-randomized, open-label, histology-stratified, two-arm interventional study evaluating Microlyvaq™, a personalized multi-epitope peptide vaccine, in combination with first-line pembrolizumab and platinum-based chemotherapy in adults with advanced or metastatic non-small cell lung cancer (NSCLC).
Patients are assigned to treatment arm according to tumor histology only (no randomization):
- Arm 1 (Squamous NSCLC): Microlyvaq™ + carboplatin AUC 5 + paclitaxel 175 mg/m² + pembrolizumab.
- Arm 2 (Non-squamous NSCLC): Microlyvaq™ + carboplatin AUC 5 + pemetrexed 500 mg/m² + pembrolizumab, with standard folate, vitamin B12, and corticosteroid premedication.
Rationale and Unmet Need Pembrolizumab plus platinum-based chemotherapy is a standard first-line option in metastatic NSCLC and improves survival compared with chemotherapy alone. However, many patients never respond, and responders often experience early progression. Current biomarkers (e.g., PD-L1 expression or tumor mutational burden) do not reliably predict durable benefit. Major causes of failure include incomplete or exhausted tumor-reactive T-cell repertoires, stromal and vascular barriers to T-cell infiltration, immunosuppressive myeloid and cytokine milieus, metabolic constraints in the tumor microenvironment, and antigenic escape under immune pressure. Releasing PD-1-mediated inhibition, even together with chemotherapy-induced antigen release, often does not generate a sustained, diversified, polyfunctional anti-tumor immune response.
Microlyvaq™ is designed to introduce into each patient a de novo, computationally defined set of tumor-directed T-cell specificities that are tailored to the individual tumor mutational and antigenic landscape, aligned with the patient's HLA genotype, and biased toward clonally important, difficult-to-lose lesions to reduce antigen-loss escape. The vaccine is administered in a prime-boost schedule intentionally synchronized with pembrolizumab and the histology-appropriate chemotherapy backbone.
The overarching early Phase I hypothesis is that a personalized multi-epitope vaccine can be safely integrated with standard chemo-immunotherapy, will induce measurable polyfunctional T-cell responses and favorable biomarker changes, and may provide preliminary signals of deeper and more durable clinical responses than would be expected with chemo-immunotherapy alone, thereby justifying later-phase studies.
Microlyvaq™ Platform (Tumor Profiling and Epitope Selection) For each participant, tumor material is analyzed using next-generation sequencing and HLA typing to generate a patient-specific pool of candidate antigens, including private neoantigens (from non-synonymous mutations, indels, fusions or splice variants) and selected tumor-associated antigens that are overexpressed in NSCLC. An AI/machine-learning-based immunogenetic scoring system evaluates each candidate epitope with respect to predicted HLA binding, processing and presentation, tumor specificity, clonality, and likelihood of immune escape. Quantum-inspired structural modeling is then used to further prioritize peptides predicted to form stable peptide-MHC complexes that are accessible to T-cell receptors. From this process, a finite panel of class I and class II peptides is selected to compose the personalized Microlyvaq™ lot for that patient.
The epitope selection algorithm is "context-aware" of the planned chemotherapy backbone (carboplatin/paclitaxel in Arm 1 vs carboplatin/pemetrexed in Arm 2), recognizing that these regimens differentially shape patterns of tumor cell death, vascular and stromal remodeling, and transient changes in lymphoid and myeloid compartments. Panels are therefore optimized with respect to both the patient's tumor biology and the expected treatment-induced immune milieu.
Manufacturing and Administration Microlyvaq™ is manufactured under Good Manufacturing Practice (GMP) conditions. Selected peptides are synthesized, purified, and blended into a multi-epitope peptide formulation, with standard identity, purity, sterility, and endotoxin testing and verification of chain-of-identity and chain-of-custody. Feasibility endpoints include the proportion of enrolled patients in whom a Microlyvaq™ lot can be successfully generated and released within a clinically relevant time window from biopsy to first vaccination, as well as logistical performance across manufacturing, storage, shipping, and on-site handling.
The vaccine is administered by subcutaneous or intradermal injection (final route defined in the protocol) in a prime-boost schedule coordinated with pembrolizumab and chemotherapy (e.g., a prime in Cycle 1 followed by boosts in subsequent cycles and, where appropriate, during pembrolizumab maintenance). Standard premedication and post-dose observation are used to monitor for local and systemic reactions.
Study Objectives and Assessments Because this is an early Phase I non-randomized trial, the primary focus is on safety, tolerability, and feasibility of integrating Microlyvaq™ into standard first-line regimens for squamous and non-squamous NSCLC. Treatment-emergent adverse events, serious adverse events, and immune-related adverse events will be collected and graded using standard criteria. Feasibility measures include adherence to the planned vaccination schedule and the ability to deliver individualized vaccine lots on time.
Key secondary and exploratory objectives include evaluation of vaccine-induced CD4⁺ and CD8⁺ T-cell responses against vaccine-encoded epitopes, T-cell receptor (TCR) repertoire dynamics (clonal expansion and persistence of vaccine-linked clonotypes), circulating tumor DNA (ctDNA) kinetics, and changes in the tumor microenvironment in patients who consent to on-treatment biopsies. Preliminary anti-tumor activity (e.g., overall response rate, duration of response, progression-free survival and overall survival per RECIST v1.1) will be described separately in each arm; the study is not powered for formal inter-arm comparisons.
Patient Population and Treatment Eligible patients are adults with advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC who are candidates for first-line pembrolizumab plus platinum-based chemotherapy according to local standards, have ECOG performance status 0-1, adequate organ function, and sufficient tumor tissue for sequencing and HLA typing. Patients with squamous histology are assigned to Arm 1; those with non-squamous histology (e.g., adenocarcinoma or large-cell) are assigned to Arm 2. Key exclusions include prior PD-1/PD-L1/CTLA-4 blockade in the metastatic setting, uncontrolled CNS metastases, and clinically significant active autoimmune disease. Full eligibility criteria are specified elsewhere in the protocol.
Safety Monitoring and Oversight Patients will undergo regular clinical evaluations, laboratory testing, and radiologic assessments. Dosing of Microlyvaq™, pembrolizumab, and chemotherapy may be withheld, modified, or discontinued according to protocol-defined criteria in the event of toxicity. Immune-related toxicities will be managed in accordance with contemporary guidelines for checkpoint inhibitors, with additional guidance for suspected vaccine-related events. An independent Data Safety Monitoring Board (DSMB) will periodically review accumulating safety, feasibility, and emerging efficacy/biomarker data and may recommend modification, temporary suspension, or early termination of one or both histology-defined arms if warranted.
Sample Size and Design Summary The initial safety cohort will enroll 12 patients who will be evaluable for toxicity. If no Microlyvaq™-related adverse event of > Grade 2 is observed in more than 3 patients and no Grade 4 Microlyvaq™-related toxicity is observed in any patient, enrollment may expand to a total of 30 patients across both non-randomized arms. Data from this early Phase I study are intended to support the feasibility, safety, and biological activity of Microlyvaq™ and to guide the design of subsequent Phase Ib/II trials in squamous and non-squamous NSCLC.
- Conditions
- NSCLC (Non-small Cell Lung Cancer), Squamous Lung Cancer With FGFR1 Amplification, Non-Squamous Non Small Cell Lung Cancer
- Being tested
- Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)
- Keywords
- Microlyvaq™, Neoantigen vaccine, Quantum molecular coupling, AI/ML-driven personalization, Th1 polyfunctional T-cell response, Pembrolizumab combination, Circulating tumor DNA (ctDNA) monitoring
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)Biological
- Investigational Intervention 1.1 Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) A patient-specific, algorithmically composed, GMP-manufactured multi-epitope immunotherapy.
Each subject's Microlyvaq™ lot is built using:
Whole exome sequencing (WES), RNA-seq of that subject's tumor, Matched normal DNA (when available), High-resolution HLA typing, AI/ML epitope immunogenicity ranking (tumor specificity, clonality, escape risk, Th1 bias), Quantum molecular coupling / stability modeling of peptide-HLA-TCR energetics.
The final product intentionally contains:
Class I-restricted epitopes (for CD8⁺ cytotoxic T cells), Class II-restricted epitopes (for CD4⁺ Th1 helper support and durability), All screened for manufacturability, sterility, and safety (GMP, QP release). Formulation / administration Multi-peptide (or peptide-adjuvant co-formulation) given intradermally/subcutaneously (route finalized in pharmacy manual).
Co-administered with a Th1-skewing immunostimulator
| Study group | Role | What they receive |
|---|---|---|
| Microlyvaq™ + carboplatin AUC 5, pemetrexed 500 mg/m2, pembrolizumab (Non-Squamous Backbone) | Active comparator | Arm A: Microlyvaq™ + Carboplatin + Pemetrexed + Pembrolizumab (Non-Squamous NSCLC) Target population: Adults with advanced/metastatic non-squamous NSCLC (adenocarcinoma, large-cell, or NSCLC-NOS adjudicated non-squamous) in the first-line systemic setting, with no prior systemic therapy for metastatic disease.
Regimen: Patients receive a personalized Microlyvaq™ multi-epitope vaccine (AI/ML- and quantum-refined, derived from tumor WES/RNA-seq and high-resolution HLA typing) administered intradermally or subcutaneously (per pharmacy manual), together with carboplatin AUC 5, pemetrexed 500 mg/m², and pembrolizumab at protocol-specified doses and schedule. Microlyvaq™ is given as a prime on Cycle 1 Day 1 (±window), with boosts around Cycle 2 (~Week 3) and Cycle 3 (~Week 6), and optional maintenance/booster doses aligned with pembrolizumab (±pemetrexed) maintenance. Receives: Biological: Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) |
| Microlyvaq™ + carboplatin AUC5, paclitaxel 175 mg/m2, pembrolizumab (Squamous-Adapted Backbone) | Active comparator | Arm A: Microlyvaq™ + carboplatin AUC5, paclitaxel 175 mg/m2, pembrolizumab (Squamous NSCLC) Target population / stratum: Adults with advanced/metastatic squamous NSCLC in the first-line systemic setting, with no prior systemic therapy for metastatic disease in this line.
Regimen: Patients receive personalized Microlyvaq™ (AI/ML-driven epitope discovery, quantum molecular stability screening, Th1-skewed design) plus carboplatin AUC 5, paclitaxel 175 mg/m², and pembrolizumab at protocol-specified doses and schedule.
Microlyvaq™ dosing follows the same core prime/boost structure as the non-squamous arm:
Prime: Cycle 1 (Day 1 ± window) Boost 1: ~Week 3 (Cycle 2) Boost 2: ~Week 6 (Cycle 3) Optional continued boosters aligned with pembrolizumab maintenance. The same observation, safety, and reactogenicity monitoring rules apply as in the non-squamous arm. Receives: Biological: Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS): AI epitope ranking, quantum energetics, TCR repertoire engineering, ctDNA collapse, spatial immune remodeling - is in service of extending OS safely. Subjects alive at cut-off are censored at last known alive.
Overall survival is the time from first dose of study treatment to death from any cause. Survival will be summarized with Kaplan-Meier curves; between-arm comparisons will use a stratified Cox model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). If non-proportional hazards are detected, restricted mean survival time (RMST) will be used. Stratification factors may include PD-L1 proportion score (TPS), smoking status, actionable driver status (EGFR/ALK/ROS1/ERBB2/KRAS-G12C), and geographic region. Subsequent anti-cancer therapy after progression will not reset survival time (treatment-policy strategy). Patients lost to follow-up will be censored at the last date known alive. Overall survival will be evaluated in two non-randomized histology cohorts: Arm 1 (squamous NSCLC): Microlyvaq™ + carboplatin + paclitaxel + pembrolizumab; Arm 2 (non-squamous NSCLC): Microlyvaq™ + carboplatin + pemetrexed + pembrolizumab (with folate/B12 and steroid support).
Measured: Survival status assessed approximately every 12 weeks during long-term follow-up, through study completion, up to approximately 36 months.
Objective Response Rate (ORR; Confirmed CR+PR): The Microlyvaq™ vaccine is delivered into a "window of susceptibility": right when chemotherapy has induced immunogenic cell death and pembrolizumab has lifted PD-1 brakes on on exhausted T cells.
- ORR (%) with 95% CI in the Full Analysis Set (all randomized with measurable disease at baseline).
- Between-arm comparison via stratified CMH or logistic regression adjusting for prespecified strata.
- Missing confirmatory scan defaults to "non-responder" in the primary analysis to avoid false inflation.
In Microlyvaq™, ORR is not just "does tumor shrink." It's "does our AI / ML / quantum-informed control signal actually force the tumor-immune system into the kill state we predicted, on schedule."• Each Microlyvaq™ lot is not a fixed commercial SKU. It's a computationally composed payload of ~17-25 epitopes, each picked for that exact patient by AI/ML plus quantum energy modeling to maximize productive peptide-HLA display, stable TCR engagement geometry, and resistance to tumor immune escape. In Microlyvaq™, ORR is not just "does tumor shrink." It's "does our AI / ML / quantum-informed signal actually force the tumor-immune system into the kill state we predicted, on schedule"
Measured: Confirmation window: Response must be confirmed 8 weeks after first CR/PR call, so typically ~Week 14 for first responders.Update cadence: Every imaging timepoint: 6 weeks through Week 24, then 12 weeks thereafter.
Secondary outcomes (6)
Progression-Free Survival (PFS): Time from randomization to first of either: 1. RECIST v1.1 progression (investigator), or 2. Death from any cause. Sensitivity analysis uses blinded ERC progression calls.
- Kaplan-Meier curves, stratified log-rank test, and stratified Cox HR with 95% CI.
- Handling of new therapy before documented PD: in the primary analysis, switching early to another systemic therapy is treated as if progression occurred at the last adequate tumor assessment; sensitivity analysis censors at switch and relies on ERC adjudication.
If PFS meaningfully improves and aligns with immune readouts (ctDNA suppression, sustained TCR clones, maintained intratumoral CD8⁺/Th1 infiltration), that's strong mechanistic validation. PFS measures whether the new immune repertoire we engineered (Th1-supported, polyfunctional, persistent TCR clonotypes) is actually able to hold the tumor in a suppressed state under real-world stress - metabolic starvation, stromal exclusion, myeloid suppression, spatial heterogeneity - once the initial cytotoxic wave is over.
Measured: Time Frame: From baseline (scan within 28 days before Day 1) through study completion, with tumor assessments every 6 weeks through Week 24, then every 12 weeks thereafter (up to approximately 24 months).
Duration of Response (DoR) for confirmed responders (CR/PR)
Duration of response (DoR) is defined, for participants with confirmed complete or partial response (CR/PR), as the time from first documented response to RECIST v1.1 progression or death; participants without an event are censored at the last adequate tumor assessment. DoR will be summarized using Kaplan-Meier curves in responders, with median DoR and 95% confidence intervals, and sensitivity analyses using independent ERC review and alternative censoring at the start of new anti-cancer therapy. Exploratory analyses may overlay ctDNA kinetics during DoR to show molecular durability alongside radiologic durability, as a readout of persistence of vaccine-induced T-cell responses and the underlying epitope-selection strategy.
Measured: From end of on-treatment follow-up, survival status assessed approximately every 12 weeks through study completion, up to approximately 36 months.
Disease Control Rate (DCR): CR + PR + durable stable disease (SD ≥6 weeks at the first scheduled post-baseline scan).
Disease Control Rate (DCR): Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) lasting ≥ 6 weeks at or beyond the first scheduled post-baseline tumor assessment, per RECIST v1.1. In metastatic NSCLC, DCR captures not only overt tumor shrinkage but also durable "immune-mediated stalemate," where Microlyvaq™ may convert immune-cold, myeloid-rich lesions into inflamed, T-cell-infiltrated tumors that stop progressing but do not fully regress.
Analysis: Proportion (with 95% confidence interval) in the full analysis set with measurable disease; between-arm comparisons using logistic regression and/or Cochran-Mantel-Haenszel (CMH) methods stratified by prespecified factors.
Measured: From the first post-baseline tumor assessment (approximately Week 6) through confirmation of disease control, with tumor assessments every 6 weeks through Week 24, then every 12 weeks thereafter through study completion (up to approximately 24
Time to Response (TTR):Among responders, time from randomization to first confirmed CR/PR.
The Microlyvaq™ prime/boost schedule is phase-matched to chemo/pembro timing windows when antigen release, checkpoint relief, and vascular access are maximized. If we got the timing right, responses shouldn't be mysteriously delayed; they should start to appear in those synchronized windows. A long lag with late "catch-up" responses might signal mis-phasing of u(t).
- Median TTR and distribution descriptions across arms.
- Non-parametric comparisons with caveats about responder-only bias.
Measured: First evaluable: First scan with CR/PR (~Week 6).Confirmation anchor: Responses are only counted once confirmed 4-8 weeks later (so confirmed TTR for early responders ~Week 10-14).
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Incidence, severity, and relationship to study treatment will be summarized by arm for all treatment-emergent adverse events (TEAEs), including Grade ≥3 TEAEs and TEAEs leading to treatment discontinuation. By-arm incidence tables and exposure-adjusted incidence rates will be presented. A narrative review will be provided for any severe systemic inflammatory TEAEs temporally associated with Microlyvaq™.
Measured: From first dose of any study drug through 30 days after the last dose of any study drug (up to approximately 12 months, depending on treatment duration).
Time to Sustained Deterioration in LC13 Lung Symptoms (Dyspnea, Cough, Chest Pain)
Time from baseline to the first ≥10-point worsening from baseline in prespecified EORTC QLQ-LC13 lung symptom items (dyspnea, cough, chest pain) that is confirmed (i.e., persists) at the next scheduled assessment; death before the next assessment is counted as deterioration in the primary analysis. This endpoint evaluates whether treatment delays clinically meaningful worsening of lung symptoms (patients breathing better, coughing less, and having less chest pain). Time to deterioration will be analyzed using Kaplan-Meier methods with stratified Cox hazard ratios and 95% confidence intervals; mixed models for repeated measures (MMRM) will be used to describe mean symptom changes over time as supportive analyses.
Measured: From baseline (Day 1) until the first sustained deterioration in LC13 score or death, whichever occurs first, assessed up to approximately 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2025
- Study start2 Feb 2026 (estimated)
- Primary completion2 Feb 2028 (estimated)
- Study completion2 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC (Non-small Cell Lung Cancer)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The Microlyvaq™ interventional study model is a non-randomized, seamless adaptive Phase II/III, histology-stratified trial in first-line advanced NSCLC. Patients are not randomized between regimens; instead, they are assigned to one of two predefined treatment arms solely on the basis of tumor histology: Arm 1 - Squamous NSCLC: Microlyvaq™ personalized multi-epitope vaccine administered in combination with carboplatin AUC 5, paclitaxel 175 mg/m², and pembrolizumab. Arm 2 - Non-squamous NSCLC: Microlyvaq™ personalized multi-epitope vaccine administered in combination with carboplatin AUC 5, pemetrexed 500 mg/m², and pembrolizumab. The intervention is not one-size-fits-all: within each non-randomized arm, each patient's Microlyvaq™ lot is uniquely generated using AI/ML-guided selection of neoantigens, followed by quantum molecular stability ("quantum immunogenetics") to prioritize epitopes predicted to be stably presented and highly immunogenic.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biogenea Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- https://interonco.gr/en/
- Responsible party
- Principal investigator, John Grigoriadis PharmDrs, Biogenea Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07285434
- Sponsor's protocol ID
- Biogenea2
- Acronym
- Microlyvaq™
- Status last verified
- Dec 2025
- First submitted
- 14 Nov 2025
- Last updated
- 16 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The following de-identified, participant-level data will be included: Core clinical efficacy data Demographics and baseline disease characteristics (e.g. age, sex, ECOG performance status, histology, PD-L1 tumor proportion score strata, presence/absence of actionable oncogenic drivers). Treatment assignment (study arm) and treatment exposure (dates and number of cycles of Microlyvaq™, pembrolizumab, platinum/taxane or pemetrexed-based chemotherapy). Tumor response assessments per RECIST v1.1 (target lesion measurements, best overall response, confirmation status). Time-to-event endpoints: progression-free survival (PFS), duration of response (DoR), overall survival (OS), and censoring information (dates and reasons). Disease control status at protocol-defined timepoints. Concomitant anti-cancer therapies received after on-study treatment discontinuation.
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of the Therapeutic Effectiveness of In-silico-Designed, Machine Learning Inspired, and Quantum-molecularly Coupled Personalized Neoantigenic Vaccines Microlyvaq™ in Patients With Advanced Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07285434
- Acronym / sponsor ID
- Microlyvaq™ / Biogenea2
- Conditions
- NSCLC (Non-small Cell Lung Cancer), Squamous Lung Cancer With FGFR1 Amplification, Non-Squamous Non Small Cell Lung Cancer
- Keywords
- Microlyvaq™, Neoantigen vaccine, Quantum molecular coupling, AI/ML-driven personalization, Th1 polyfunctional T-cell response, Pembrolizumab combination, Circulating tumor DNA (ctDNA) monitoring
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Biogenea Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Collaborators
- https://interonco.gr/en/
- Study start
- 2 Feb 2026 (estimated)
- Primary completion
- 2 Feb 2028 (estimated)
- Study completion
- 2 Feb 2030 (estimated)
- First posted
- 16 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Microlyvaq™ is a first-line, non-randomized, two-arm clinical trial in advanced non-small cell lung cancer (NSCLC). In both arms, patients receive a personalized multi-epitope vaccine (Microlyvaq™) on top of standard-of-care chemo-immunotherapy, with treatment tailored by histology:
Arm 1 - Squamous NSCLC: Microlyvaq™ + carboplatin AUC 5 + paclitaxel 175 mg/m² + pembrolizumab Arm 2 - Non-squamous NSCLC: Microlyvaq™ + carboplatin AUC 5 + pemetrexed 500 mg/m² + pembrolizumab Because this is a non-randomized study, patients are assigned to arms based on tumor histology (squamous vs non-squamous), not by random allocation.
The core problem it addresses is that even with pembrolizumab plus histology-appropriate chemotherapy, many patients either never respond or respond briefly and then progress. Tumors evade by exhausting T cells, excluding them from the tumor bed, evolving antigen loss, and maintaining suppressive myeloid and stromal niches. Microlyvaq™ is designed to overcome these resistance modes by actively installing new, durable, polyfunctional anti-tumor immunity rather than relying only on pre-existing T cells.
Here's how it works. Each patient's tumor is sequenced (whole exome and RNA-seq) to identify both well-known lung cancer-associated antigens (e.g. NY-ESO-1, SOX2, p53, MAGE-A4, BRAF, BMI1, FXR1, HuD, HuC, CAGE) and private neoantigens created by that tumor's specific mutations, fusions, and splice variants. From this large antigen pool, machine learning models score each candidate epitope for that specific patient. The models consider predicted HLA class I and II presentation, how efficiently the antigen will actually be processed and displayed, whether it's expressed in tumor but not healthy tissue, how essential it is to most malignant cells (to avoid easy escape), and whether it is likely to drive functional, non-exhausted T-cell responses. This is not a generic ranking; it is individualized per patient.
The most promising epitopes then undergo a quantum molecular coupling evaluation. Instead of simply asking whether a peptide binds a given HLA, Microlyvaq™ modeling simulates the peptide-MHC complex as a physical system and approximates solutions to Ĥψ = Eψ to estimate whether the peptide will form a stable, low-energy, presentation-competent conformation that a realistic T-cell receptor can dock to without high energetic penalty. Epitopes that look good in simple binding screens but are predicted to be unstable, transient, or geometrically inaccessible to TCRs are excluded. The remaining epitope set is engineered to: (1) recruit potent CD8⁺ cytotoxic T cells that can kill tumor cells, and (2) recruit CD4⁺ Th1 helper T cells that produce IFN-γ, TNF-α, and IL-2 to sustain and support those killers. The vaccine is therefore intentionally multi-epitope, Th1-biased, and patient-specific.
Each personalized Microlyvaq™ lot is manufactured under GMP and given as a prime-boost series in sync with pembrolizumab and the appropriate chemotherapy backbone for the patient's histologic arm (carboplatin/paclitaxel for squamous; carboplatin/pemetrexed for non-squamous). Timing is deliberate: chemotherapy induces immunogenic tumor cell death and antigen release and transiently "opens up" the tumor microenvironment, while pembrolizumab lifts PD-1-mediated brakes on emerging T cells. Microlyvaq™ is dosed into that vulnerable window to expand vaccine-encoded clones just as new antigen is exposed and suppression is partially relieved. The goal is to generate rapid tumor shrinkage, then sustained immune pressure on residual disease, plus epitope spreading - where the immune system begins to recognize additional tumor targets beyond those in the vaccine, making escape more difficult.
The trial itself is structured as a seamless, adaptive, non-randomized Phase I/IIa study, with two predefined histology-based arms (squamous vs non-squamous) rather than randomized treatment allocations. The primary early endpoint is objective response rate (RECIST v1.1). Key secondary endpoints include progression-free survival, duration of response, and overall survival. In addition, the study incorporates real-time translational signals as decision points, including:
- polyfunctional Th1 and CD8⁺ responses to vaccine epitopes by ELISpot/ICS,
- durable expansion and persistence of vaccine-linked TCR clonotypes in blood and, when feasible, in tumor,
- rapid decline in circulating tumor DNA as an early molecular marker of tumor clearance,
- improved tumor infiltration by CD8⁺ and Th1 cells, and
- remodeling of the tumor microenvironment away from suppressive myeloid states. If a given histology arm shows strong clinical responses plus these immune/molecular signals, that arm can seamlessly expand into survival-powered confirmation. If it does not, predefined futility rules allow that arm to stop, all within this non-randomized, adaptive framework.
Detailed description
This is an early Phase I, non-randomized, open-label, histology-stratified, two-arm interventional study evaluating Microlyvaq™, a personalized multi-epitope peptide vaccine, in combination with first-line pembrolizumab and platinum-based chemotherapy in adults with advanced or metastatic non-small cell lung cancer (NSCLC).
Patients are assigned to treatment arm according to tumor histology only (no randomization):
- Arm 1 (Squamous NSCLC): Microlyvaq™ + carboplatin AUC 5 + paclitaxel 175 mg/m² + pembrolizumab.
- Arm 2 (Non-squamous NSCLC): Microlyvaq™ + carboplatin AUC 5 + pemetrexed 500 mg/m² + pembrolizumab, with standard folate, vitamin B12, and corticosteroid premedication.
Rationale and Unmet Need Pembrolizumab plus platinum-based chemotherapy is a standard first-line option in metastatic NSCLC and improves survival compared with chemotherapy alone. However, many patients never respond, and responders often experience early progression. Current biomarkers (e.g., PD-L1 expression or tumor mutational burden) do not reliably predict durable benefit. Major causes of failure include incomplete or exhausted tumor-reactive T-cell repertoires, stromal and vascular barriers to T-cell infiltration, immunosuppressive myeloid and cytokine milieus, metabolic constraints in the tumor microenvironment, and antigenic escape under immune pressure. Releasing PD-1-mediated inhibition, even together with chemotherapy-induced antigen release, often does not generate a sustained, diversified, polyfunctional anti-tumor immune response.
Microlyvaq™ is designed to introduce into each patient a de novo, computationally defined set of tumor-directed T-cell specificities that are tailored to the individual tumor mutational and antigenic landscape, aligned with the patient's HLA genotype, and biased toward clonally important, difficult-to-lose lesions to reduce antigen-loss escape. The vaccine is administered in a prime-boost schedule intentionally synchronized with pembrolizumab and the histology-appropriate chemotherapy backbone.
The overarching early Phase I hypothesis is that a personalized multi-epitope vaccine can be safely integrated with standard chemo-immunotherapy, will induce measurable polyfunctional T-cell responses and favorable biomarker changes, and may provide preliminary signals of deeper and more durable clinical responses than would be expected with chemo-immunotherapy alone, thereby justifying later-phase studies.
Microlyvaq™ Platform (Tumor Profiling and Epitope Selection) For each participant, tumor material is analyzed using next-generation sequencing and HLA typing to generate a patient-specific pool of candidate antigens, including private neoantigens (from non-synonymous mutations, indels, fusions or splice variants) and selected tumor-associated antigens that are overexpressed in NSCLC. An AI/machine-learning-based immunogenetic scoring system evaluates each candidate epitope with respect to predicted HLA binding, processing and presentation, tumor specificity, clonality, and likelihood of immune escape. Quantum-inspired structural modeling is then used to further prioritize peptides predicted to form stable peptide-MHC complexes that are accessible to T-cell receptors. From this process, a finite panel of class I and class II peptides is selected to compose the personalized Microlyvaq™ lot for that patient.
The epitope selection algorithm is "context-aware" of the planned chemotherapy backbone (carboplatin/paclitaxel in Arm 1 vs carboplatin/pemetrexed in Arm 2), recognizing that these regimens differentially shape patterns of tumor cell death, vascular and stromal remodeling, and transient changes in lymphoid and myeloid compartments. Panels are therefore optimized with respect to both the patient's tumor biology and the expected treatment-induced immune milieu.
Manufacturing and Administration Microlyvaq™ is manufactured under Good Manufacturing Practice (GMP) conditions. Selected peptides are synthesized, purified, and blended into a multi-epitope peptide formulation, with standard identity, purity, sterility, and endotoxin testing and verification of chain-of-identity and chain-of-custody. Feasibility endpoints include the proportion of enrolled patients in whom a Microlyvaq™ lot can be successfully generated and released within a clinically relevant time window from biopsy to first vaccination, as well as logistical performance across manufacturing, storage, shipping, and on-site handling.
The vaccine is administered by subcutaneous or intradermal injection (final route defined in the protocol) in a prime-boost schedule coordinated with pembrolizumab and chemotherapy (e.g., a prime in Cycle 1 followed by boosts in subsequent cycles and, where appropriate, during pembrolizumab maintenance). Standard premedication and post-dose observation are used to monitor for local and systemic reactions.
Study Objectives and Assessments Because this is an early Phase I non-randomized trial, the primary focus is on safety, tolerability, and feasibility of integrating Microlyvaq™ into standard first-line regimens for squamous and non-squamous NSCLC. Treatment-emergent adverse events, serious adverse events, and immune-related adverse events will be collected and graded using standard criteria. Feasibility measures include adherence to the planned vaccination schedule and the ability to deliver individualized vaccine lots on time.
Key secondary and exploratory objectives include evaluation of vaccine-induced CD4⁺ and CD8⁺ T-cell responses against vaccine-encoded epitopes, T-cell receptor (TCR) repertoire dynamics (clonal expansion and persistence of vaccine-linked clonotypes), circulating tumor DNA (ctDNA) kinetics, and changes in the tumor microenvironment in patients who consent to on-treatment biopsies. Preliminary anti-tumor activity (e.g., overall response rate, duration of response, progression-free survival and overall survival per RECIST v1.1) will be described separately in each arm; the study is not powered for formal inter-arm comparisons.
Patient Population and Treatment Eligible patients are adults with advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC who are candidates for first-line pembrolizumab plus platinum-based chemotherapy according to local standards, have ECOG performance status 0-1, adequate organ function, and sufficient tumor tissue for sequencing and HLA typing. Patients with squamous histology are assigned to Arm 1; those with non-squamous histology (e.g., adenocarcinoma or large-cell) are assigned to Arm 2. Key exclusions include prior PD-1/PD-L1/CTLA-4 blockade in the metastatic setting, uncontrolled CNS metastases, and clinically significant active autoimmune disease. Full eligibility criteria are specified elsewhere in the protocol.
Safety Monitoring and Oversight Patients will undergo regular clinical evaluations, laboratory testing, and radiologic assessments. Dosing of Microlyvaq™, pembrolizumab, and chemotherapy may be withheld, modified, or discontinued according to protocol-defined criteria in the event of toxicity. Immune-related toxicities will be managed in accordance with contemporary guidelines for checkpoint inhibitors, with additional guidance for suspected vaccine-related events. An independent Data Safety Monitoring Board (DSMB) will periodically review accumulating safety, feasibility, and emerging efficacy/biomarker data and may recommend modification, temporary suspension, or early termination of one or both histology-defined arms if warranted.
Sample Size and Design Summary The initial safety cohort will enroll 12 patients who will be evaluable for toxicity. If no Microlyvaq™-related adverse event of > Grade 2 is observed in more than 3 patients and no Grade 4 Microlyvaq™-related toxicity is observed in any patient, enrollment may expand to a total of 30 patients across both non-randomized arms. Data from this early Phase I study are intended to support the feasibility, safety, and biological activity of Microlyvaq™ and to guide the design of subsequent Phase Ib/II trials in squamous and non-squamous NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The Microlyvaq™ interventional study model is a non-randomized, seamless adaptive Phase II/III, histology-stratified trial in first-line advanced NSCLC. Patients are not randomized between regimens; instead, they are assigned to one of two predefined treatment arms solely on the basis of tumor histology: Arm 1 - Squamous NSCLC: Microlyvaq™ personalized multi-epitope vaccine administered in combination with carboplatin AUC 5, paclitaxel 175 mg/m², and pembrolizumab. Arm 2 - Non-squamous NSCLC: Microlyvaq™ personalized multi-epitope vaccine administered in combination with carboplatin AUC 5, pemetrexed 500 mg/m², and pembrolizumab. The intervention is not one-size-fits-all: within each non-randomized arm, each patient's Microlyvaq™ lot is uniquely generated using AI/ML-guided selection of neoantigens, followed by quantum molecular stability ("quantum immunogenetics") to prioritize epitopes predicted to be stably presented and highly immunogenic.
| Arm | Type | Receives |
|---|---|---|
| Microlyvaq™ + carboplatin AUC 5, pemetrexed 500 mg/m2, pembrolizumab (Non-Squamous Backbone) | Active comparator | Biological: Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)Arm A: Microlyvaq™ + Carboplatin + Pemetrexed + Pembrolizumab (Non-Squamous NSCLC) Target population: Adults with advanced/metastatic non-squamous NSCLC (adenocarcinoma, large-cell, or NSCLC-NOS adjudicated non-squamous) in the first-line systemic setting, with no prior systemic therapy for metastatic disease. Regimen: Patients receive a personalized Microlyvaq™ multi-epitope vaccine (AI/ML- and quantum-refined, derived from tumor WES/RNA-seq and high-resolution HLA typing) administered intradermally or subcutaneously (per pharmacy manual), together with carboplatin AUC 5, pemetrexed 500 mg/m², and pembrolizumab at protocol-specified doses and schedule. Microlyvaq™ is given as a prime on Cycle 1 Day 1 (±window), with boosts around Cycle 2 (~Week 3) and Cycle 3 (~Week 6), and optional maintenance/booster doses aligned with pembrolizumab (±pemetrexed) maintenance. |
| Microlyvaq™ + carboplatin AUC5, paclitaxel 175 mg/m2, pembrolizumab (Squamous-Adapted Backbone) | Active comparator | Biological: Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)Arm A: Microlyvaq™ + carboplatin AUC5, paclitaxel 175 mg/m2, pembrolizumab (Squamous NSCLC) Target population / stratum: Adults with advanced/metastatic squamous NSCLC in the first-line systemic setting, with no prior systemic therapy for metastatic disease in this line. Regimen: Patients receive personalized Microlyvaq™ (AI/ML-driven epitope discovery, quantum molecular stability screening, Th1-skewed design) plus carboplatin AUC 5, paclitaxel 175 mg/m², and pembrolizumab at protocol-specified doses and schedule. Microlyvaq™ dosing follows the same core prime/boost structure as the non-squamous arm: Prime: Cycle 1 (Day 1 ± window) Boost 1: ~Week 3 (Cycle 2) Boost 2: ~Week 6 (Cycle 3) Optional continued boosters aligned with pembrolizumab maintenance. The same observation, safety, and reactogenicity monitoring rules apply as in the non-squamous arm. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (30 listed)
- -
- Age
- ≥18 years at the time of informed consent. Diagnosis / Histology
- Non-squamous (e.g. adenocarcinoma, large-cell, NSCLC-NOS adjudicated non-squamous), or Squamous (if/when that stratum is open). Diagnosis must be locally documented and source-verifiable. Stage / Disease Status Stage IIIB / IIIC / IV or recurrent/metastatic NSCLC not amenable to curative surgery or radiotherapy, per AJCC 8th edition staging.
- No prior systemic therapy for advanced/metastatic disease in this line. Prior adjuvant/neoadjuvant therapy or consolidation chemo-RT is allowed if completed and the subject relapsed outside the protocol-defined disease-free interval (e.g. relapse ≥6-12 months after completion, per final protocol text).
Key exclusion criteria (47 listed)
- Prior Systemic Therapy in Metastatic Setting Any prior systemic therapy for metastatic / unresectable NSCLC in the current line.
- Exception: prior adjuvant/neoadjuvant chemo, IO, or chemoradiation allowed if relapse occurred outside the protocol's defined exclusion interval (e.g. relapse ≥6-12 months after completion); exact interval to be specified.
- Known Oncogene-Addicted Disease Requiring Targeted SOC Subjects whose tumors harbor actionable drivers for which an approved targeted therapy is standard first-line care (e.g. EGFR activating mutation, ALK rearrangement, ROS1 rearrangement, certain ERBB2/HER2 drivers, MET exon 14 skipping, RET fusion, NTRK fusion, KRAS G12C where local standard is targeted frontline) may be excluded or enrolled only in specific sub-cohorts if allowed by the statistical design.
- Rationale: It may be unethical to withhold proven first-line targeted agents. The final protocol will define whether these genotypes are (a) excluded, (b) stratified, or (c) routed to a molecularly restricted exploratory cohort.
- Uncontrolled CNS Disease Active, symptomatic brain metastases or leptomeningeal disease requiring immediate local intervention.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic)1. Investigational Intervention 1.1 Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) A patient-specific, algorithmically composed, GMP-manufactured multi-epitope immunotherapy. Each subject's Microlyvaq™ lot is built using: Whole exome sequencing (WES), RNA-seq of that subject's tumor, Matched normal DNA (when available), High-resolution HLA typing, AI/ML epitope immunogenicity ranking (tumor specificity, clonality, escape risk, Th1 bias), Quantum molecular coupling / stability modeling of peptide-HLA-TCR energetics. The final product intentionally contains: Class I-restricted epitopes (for CD8⁺ cytotoxic T cells), Class II-restricted epitopes (for CD4⁺ Th1 helper support and durability), All screened for manufacturability, sterility, and safety (GMP, QP release). Formulation / administration Multi-peptide (or peptide-adjuvant co-formulation) given intradermally/subcutaneously (route finalized in pharmacy manual). Co-administered with a Th1-skewing immunostimulator | Biological | Microlyvaq™ + carboplatin AUC 5, pemetrexed 500 mg/m2, pembrolizumab (Non-Squamous Backbone), Microlyvaq™ + carboplatin AUC5, paclitaxel 175 mg/m2, pembrolizumab (Squamous-Adapted Backbone) |
Primary outcome
Overall Survival (OS): AI epitope ranking, quantum energetics, TCR repertoire engineering, ctDNA collapse, spatial immune remodeling - is in service of extending OS safely. Subjects alive at cut-off are censored at last known alive.
Time frame: Survival status assessed approximately every 12 weeks during long-term follow-up, through study completion, up to approximately 36 months.
Overall survival is the time from first dose of study treatment to death from any cause. Survival will be summarized with Kaplan-Meier curves; between-arm comparisons will use a stratified Cox model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). If non-proportional hazards are detected, restricted mean survival time (RMST) will be used. Stratification factors may include PD-L1 proportion score (TPS), smoking status, actionable driver status (EGFR/ALK/ROS1/ERBB2/KRAS-G12C), and geographic region. Subsequent anti-cancer therapy after progression will not reset survival time (treatment-policy strategy). Patients lost to follow-up will be censored at the last date known alive. Overall survival will be evaluated in two non-randomized histology cohorts: Arm 1 (squamous NSCLC): Microlyvaq™ + carboplatin + paclitaxel + pembrolizumab; Arm 2 (non-squamous NSCLC): Microlyvaq™ + carboplatin + pemetrexed + pembrolizumab (with folate/B12 and steroid support).
Objective Response Rate (ORR; Confirmed CR+PR): The Microlyvaq™ vaccine is delivered into a "window of susceptibility": right when chemotherapy has induced immunogenic cell death and pembrolizumab has lifted PD-1 brakes on on exhausted T cells.
Time frame: Confirmation window: Response must be confirmed 8 weeks after first CR/PR call, so typically ~Week 14 for first responders.Update cadence: Every imaging timepoint: 6 weeks through Week 24, then 12 weeks thereafter.
* ORR (%) with 95% CI in the Full Analysis Set (all randomized with measurable disease at baseline). * Between-arm comparison via stratified CMH or logistic regression adjusting for prespecified strata. * Missing confirmatory scan defaults to "non-responder" in the primary analysis to avoid false inflation. In Microlyvaq™, ORR is not just "does tumor shrink." It's "does our AI / ML / quantum-informed control signal actually force the tumor-immune system into the kill state we predicted, on schedule."• Each Microlyvaq™ lot is not a fixed commercial SKU. It's a computationally composed payload of ~17-25 epitopes, each picked for that exact patient by AI/ML plus quantum energy modeling to maximize productive peptide-HLA display, stable TCR engagement geometry, and resistance to tumor immune escape. In Microlyvaq™, ORR is not just "does tumor shrink." It's "does our AI / ML / quantum-informed signal actually force the tumor-immune system into the kill state we predicted, on schedule"
6 secondary outcomes
Progression-Free Survival (PFS): Time from randomization to first of either: 1. RECIST v1.1 progression (investigator), or 2. Death from any cause. Sensitivity analysis uses blinded ERC progression calls.
Time frame: Time Frame: From baseline (scan within 28 days before Day 1) through study completion, with tumor assessments every 6 weeks through Week 24, then every 12 weeks thereafter (up to approximately 24 months).
Duration of Response (DoR) for confirmed responders (CR/PR)
Time frame: From end of on-treatment follow-up, survival status assessed approximately every 12 weeks through study completion, up to approximately 36 months.
Disease Control Rate (DCR): CR + PR + durable stable disease (SD ≥6 weeks at the first scheduled post-baseline scan).
Time frame: From the first post-baseline tumor assessment (approximately Week 6) through confirmation of disease control, with tumor assessments every 6 weeks through Week 24, then every 12 weeks thereafter through study completion (up to approximately 24
Time to Response (TTR):Among responders, time from randomization to first confirmed CR/PR.
Time frame: First evaluable: First scan with CR/PR (~Week 6).Confirmation anchor: Responses are only counted once confirmed 4-8 weeks later (so confirmed TTR for early responders ~Week 10-14).
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of any study drug through 30 days after the last dose of any study drug (up to approximately 12 months, depending on treatment duration).
Time to Sustained Deterioration in LC13 Lung Symptoms (Dyspnea, Cough, Chest Pain)
Time frame: From baseline (Day 1) until the first sustained deterioration in LC13 score or death, whichever occurs first, assessed up to approximately 24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2025.
- Individual participant dataSharing planned: Yes. The following de-identified, participant-level data will be included: Core clinical efficacy data Demographics and baseline disease characteristics (e.g. age, sex, ECOG performance status, histology, PD-L1 tumor proportion score strata, presence/absence of actionable oncogenic drivers). Treatment assignment (study arm) and treatment exposure (dates and number of cycles of Microlyvaq™, pembrolizumab, platinum/taxane or pemetrexed-based chemotherapy). Tumor response assessments per RECIST v1.1 (target lesion measurements, best overall response, confirmation status). Time-to-event endpoints: progression-free survival (PFS), duration of response (DoR), overall survival (OS), and censoring information (dates and reasons). Disease control status at protocol-defined timepoints. Concomitant anti-cancer therapies received after on-study treatment discontinuation.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Microlyvaq™ (Personalized Multi-Epitope Immunotherapeutic) in people with NSCLC (Non-small Cell Lung Cancer) and Squamous Lung Cancer With FGFR1 Amplification, run by Biogenea Pharmaceuticals Ltd. at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS): AI epitope ranking, quantum energetics, TCR repertoire engineering, ctDNA collapse, spatial immune remodeling - is in service of extending OS safely. Subjects alive at cut-off are censored at last known alive. (time frame: Survival status assessed approximately every 12 weeks during long-term follow-up, through study completion, up to approximately 36 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.