Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2022-002805-90
    Sponsor's Protocol Code Number:EOCRC2-22
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-01-16
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2022-002805-90
    A.3Full title of the trial
    A global multicenter phase 1/2 trial of EO4010, a novel microbial-derived peptide therapeutic vaccine, in combination with nivolumab, for treatment of patients with previously treated metastatic colorectal carcinoma (the "AUDREY" study).
    Ensayo global y multicéntrico en fase I/II de EO4010, una nueva vacuna terapéutica peptídica de origen microbiano, en combinación con nivolumab, para el tratamiento de pacientes con carcinoma colorrectal metastásico previamente tratado (estudio “AUDREY”)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to investigate EO4010, a novel cancer vaccine therapy, with an immune checkpoint blocker, in patients with previously treated metastatic colorectal carcinoma.
    Un ensayo clínico para investigar EO4010, una nueva terapia de vacuna contra el cáncer, con un bloqueador de puntos de control inmunológico, en pacientes con carcinoma colorrectal metastásico previamente tratado.
    A.3.2Name or abbreviated title of the trial where available
    AUDREY study
    el estudio "AUDREY"
    A.4.1Sponsor's protocol code numberEOCRC2-22
    A.5.4Other Identifiers
    Name:INDNumber:28848
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEnterome SA
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEnterome SA
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEnterome SA
    B.5.2Functional name of contact pointMedical
    B.5.3 Address:
    B.5.3.1Street Address94/96 avenue Ledru-Rollin
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75011
    B.5.3.4CountryFrance
    B.5.4Telephone number+33614310759
    B.5.6E-mailmedicalmonitoring-crc@enterome.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEO4010
    D.3.2Product code EO4010
    D.3.4Pharmaceutical form Emulsion for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInjection (Noncurrent)
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeEO2317
    D.3.9.3Other descriptive nameEO2317
    D.3.9.4EV Substance CodeSUB205543
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeEO2318
    D.3.9.3Other descriptive nameEO2318
    D.3.9.4EV Substance CodeSUB205544
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeOMP10
    D.3.9.3Other descriptive nameOMP10
    D.3.9.4EV Substance CodeSUB290661
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeOMP11
    D.3.9.3Other descriptive nameOMP11
    D.3.9.4EV Substance CodeSUB290663
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeOMP12
    D.3.9.3Other descriptive nameOMP12
    D.3.9.4EV Substance CodeSUB290662
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codeUCP2
    D.3.9.3Other descriptive nameUCP2
    D.3.9.4EV Substance CodeSUB205542
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Opdivo
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNivolumab
    D.3.2Product code BMS-936558 D.3.3
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.3Other descriptive nameNivolumab
    D.3.9.4EV Substance CodeSUB122750
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with unresectable, previously treated locally advanced or metastatic colorectal carcinoma.
    Pacientes con carcinoma colorrectal localmente avanzado o metastásico no resecable y previamente tratado.
    E.1.1.1Medical condition in easily understood language
    Patients with locally advanced or metastatic colorectal cancer who have been previsouly treated.
    Pacientes con cáncer colorrectal localmente avanzado o metastásico que han sido tratados previamente.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052358
    E.1.2Term Colorectal cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10010036
    E.1.2Term Colorectal carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this trial is to evaluate safety and tolerability of EO4010 in combination with nivolumab in patients with unresectable, previously treated locally advanced or metastatic colorectal carcinoma.
    El objetivo principal de este ensayo es evaluar la seguridad y la tolerabilidad de EO4010 en combinación con nivolumab en pacientes con CCR localmente avanzado o metastásico irresecable, que han recibido tratamiento previamente.
    E.2.2Secondary objectives of the trial
    1. Immunogenicity in relation to T cells of EO2317, EO2318, OMP10, OMP11, OMP12, and UCP2 that compose EO4010; T cell cross-reactivity with the human TAAs FOXM1, BIRC5/survivin, UBE2C, CDC20, and KIF2C will also be evaluated,
    2. Objective response rate (ORR), disease control rate (DCR), time to response (TTR), and duration of response (DOR),
    3. Progression-free survival (PFS) and PFS rate at 4 months, and
    4. Overall survival (OS).
    1. Inmunogenia en relación con los linfocitos T de EO2317, EO2318, OMP10, OMP11, OMP12 y UCP2 que componen EO4010. También se evaluará la reactividad cruzada de los linfocitos T con los AAT humanos BIRC5/survivina, FOXM1, UBE2C, CDC20 y KIF2C,
    2. La tasa de respuesta objetiva (TRO), la tasa de control de la enfermedad (TCE), el tiempo de respuesta (TR), la duración de la respuesta (DR),
    3. La supervivencia sin progresión (SSP), así como la tasa de SSP a los 4 meses, y
    4. La supervivencia global (SG).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provided written informed consent prior to any study-related procedures (initial consent is for screening part #1 procedures, and a second consent is for screening part #2 procedures; see Protocol Section 7.2 and Section 7.3, respectively). Patients must be able to understand and be willing to sign a written informed consent.
    2. Histological confirmation of advanced non-resectable colorectal adenocarcinoma (confirmation at initial diagnosis is sufficient) which is mismatch repair proficient and microsatellite stable (according to local site standard testing procedures), i.e. patients with mismatch repair deficient or microsatellite instability-high metastatic disease cannot be recruited to this trial.
    3. Patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for (according to the judgement of the recruiting site physician; e.g., due to progression or unacceptable toxicity on the type of treatment, or type of treatment not indicated in the specific patient due to his/her disease characteristics - when appropriate a collaborative discussion between the recruiting physician and the Medical Monitor should be held to keep the study population consistent), therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.
    4. Progression during or within 3 months following the latest administration of standard therapies as outlined in inclusion criterion #3.
    5. Age ≥ 18 years old.
    6. Human leukocyte antigen (HLA)-A2 positive.
    7. ECOG performance status 0 or 1 (see Protocol Section 12.1).
    8. Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria (RECIST), version 1.1.
    9. Patients with a life expectancy of at least 3 months as judged by the recruiting site physician.
    10. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to randomization.
    11. Considering the embryofetal toxicity of the immune checkpoint inhibitor (ICI) shown in animals’ models, the following recommendations for contraception must be followed:
    a. If not surgically sterile, female patients of childbearing potential age must use highly effective contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective contraception includes (according to Clinical Trial Facilitation Group: Recommendations related to contraception and pregnancy testing in clinical trials):
    i. combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal,
    ii. progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable,
    iii. intrauterine device (IUD),
    iv. intrauterine hormone-releasing system (IUS),
    v. bilateral tubal occlusion,
    vi. vasectomized partner, and
    vii. sexual abstinence when in line with the preferred and usual lifestyle of the patient (e.g. periodic abstinence is not considered a highly effective method).
    In each case of delayed menstrual period (over 1 month between menstruations), confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles.
    b. If not surgically sterile, male with female partner of childbearing potential age must use condom from signing the ICF through 6 months after the last treatment dose administered. Males must ensure that their partners of childbearing potential use highly effective contraception also. Note, the contraception guidelines for males are not related to nivolumab but kept as a conservative precaution in this early development protocol in relation to EO4010.
    12. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
    1. Haber entregado un consentimiento informado por escrito antes de participar en cualquier procedimiento relacionado con el estudio (el consentimiento inicial es para los procedimientos de selección de la parte n.º 1 y el segundo consentimiento para los procedimientos de selección de la parte n.º 2; consulte el apartado 7.2 y el apartado 7.3 del protocolo, respectivamente). Los pacientes tendrán que entender y firmar un consentimiento informado por escrito.
    2. Confirmación histológica de adenocarcinoma colorrectal irresecable avanzado (basta con la confirmación en el diagnóstico inicial) que se produce con alteración de la vía reparadora y estable en microsatélites (de acuerdo con los procedimientos de prueba estándar del centro local), es decir, los pacientes con enfermedad con alto grado de metástasis y deficiencia en alteración de la vía reparadora o alta inestabilidad de microsatélites no podrán participar en este ensayo.
    3. Pacientes con cáncer colorrectal metastásico que han recibido tratamiento anteriormente, o no son considerados candidatos para terapias que incluyen quimioterapias a base de fluoropirimidina, oxaliplatino e irinotecán, agentes anti-VEGF y agentes anti-EGFR (según el criterio del médico del centro de selección; p. ej., debido a progresión o toxicidad inaceptable en el tipo de tratamiento, o tipo de tratamiento no indicado para el paciente concreto debido a las características de su enfermedad; cuando corresponda, el médico encargado de la selección y el supervisor médico se reunirán para comentar y mantener la coherencia de la población del estudio).
    4. Progresión durante los 3 meses posteriores a la última administración de tratamientos habituales como se describe en el criterio de inclusión n.º 3.
    5. Edad ≥ 18 años.
    6. Positivos a la presencia del antígeno leucocitario humano (HLA)-A2.
    7. Estado funcional ECOG 0 o 1 (véase el apartado 12.1 del protocolo).
    8. Enfermedad mensurable según los criterios de Response Evaluation Criteria in Solid Tumors (RECIST), versión 1.1.
    9. Pacientes con una esperanza de vida de al menos 3 meses según el criterio del médico del centro de selección.
    10. Las pacientes en edad fértil deben dar negativo en una prueba de embarazo durante las 72 horas previas a la aleatorización.
    11. Teniendo en cuenta la toxicidad embriofetal del inhibidor del punto de control inmunitario (ICI) mostrada en modelos animales, se deben seguir las siguientes recomendaciones para la anticoncepción:
    a. En caso de no ser estériles quirúrgicamente, las pacientes en edad fértil deben usar métodos anticonceptivos muy eficaces desde el momento en que firmen el formulario de consentimiento informado (FCI) hasta 6 meses después de recibir la última dosis de tratamiento administrada. Los métodos anticonceptivos de alta eficacia incluyen (según el Clinical Trial Facilitation Group): Recomendaciones relacionadas con la anticoncepción y las pruebas de embarazo en ensayos clínicos (Heads of Medicines Agencies: Clinical Trials Facilitation and Coordination Group, n.d.)):
    i. anticonceptivos hormonales mixtos (que contengan estrógeno y progesterona) asociados a la inhibición de la ovulación: orales, intravaginales o transdérmicos,
    ii. métodos anticonceptivos hormonales solo con progesterona que inhiben la ovulación: oral, inyectable o implantable,
    iii. dispositivo intrauterino (DIU),
    iv. sistema intrauterino de liberación hormonal (SIU),
    v. ligadura de trompas bilateral,
    vi. pareja vasectomizada, y
    vii. abstinencia sexual cuando sea coherente con el estilo de vida habitual preferido por el paciente (por ejemplo, la abstinencia periódica no se considera un método de alta eficacia).
    En cada caso de retraso del período menstrual (más de 1 mes entre menstruaciones), se recomienda una prueba que confirme que no está embarazada. Esta recomendación también se aplica a las mujeres en edad fértil con ciclos menstruales poco frecuentes o irregulares.
    b. Si no está esterilizado quirúrgicamente, el hombre con pareja femenina en edad fértil debe usar preservativo desde el momento en que firme el FCI hasta 6 meses después de recibir la última dosis de tratamiento administrada. Los hombres deben asegurarse de que sus parejas en edad fértil también usen métodos anticonceptivos de alta eficacia. Recuerde que las directrices de anticoncepción para hombres no están relacionadas con nivolumab, pero se mantienen como precaución conservadora en este protocolo de desarrollo temprano en relación con EO4010.
    12. Pacientes que estén dispuestos y sean capaces de cumplir el calendario de visitas, el plan de tratamiento, las pruebas analíticas y otros procedimientos del estudio indicados en el protocolo.
    E.4Principal exclusion criteria
    1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone) within 14 days before randomization, unless required to treat an adverse event (AE).
    2. Patients treated with radiotherapy within 12 weeks, and cytotoxic chemotherapy therapy within 28 days (or 5 half lives of the compound(s) administered if longer) before study treatment start.
    3. Patients with persistent Grade ≥ 2 toxicities (according to NCI-CTCAE v5.0). Toxicities must be resolved for at least 2 weeks to Grade 1 or less. However, alopecia, neuropathy, and other persisting toxicities not constituting a safety risk based on Investigator’s judgment are acceptable.
    4. Patients who have received any prior treatment with compounds targeting PD1, PD-L1, CTLA-4, or similar compounds where general resistance against therapeutic vaccination approaches might have developed.
    5. Patients who have previously received trifluridine/tipiracil (TAS-102) or regorafenib.
    6. Patients with prior exposure to EO2401, EO2040, or EO4010, i.e. therapeutic vaccine compounds including all or some components of EO4010, the current trial compound.
    7. Patients with the following abnormal laboratory values:
    a. Lymphocyte count decreased, grade 2 (lymphocytes <800 - 500/mm3; <0.8 - 0.5 x 10^9/L), or worse grade.
    b. Hemoglobin < 10 g/dL (6.2 mmol/L); transfusion is acceptable to reach the value.
    c. Absolute neutrophil count decrease (<1.5 x10^9/L).
    d. Platelet count decrease (< 75 ×10^9/L).
    e. Total bilirubin > 1.5 ×upper limit of normal (ULN; according to the performing laboratory’s reference ranges); except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 xULN.
    f. Alanine aminotransferase (ALT) > 3 ×ULN; if disease metastatic to the liver > 5 xULN.
    g. Aspartate aminotransferase (AST) > 3 ×ULN; if disease metastatic to the liver > 5 xULN.
    h. Serum creatinine increase (> 1.5 ×ULN).
    i. Abnormal thyroid function per local laboratory levels;
    8. Other malignancy or prior malignancy with a disease-free interval of less than 3 years prior to ICF signing; except those treated with surgical intervention and an expected low likelihood of recurrence such as basal cell or squamous cell skin cancer, or carcinoma in situ.
    9. Patients with clinically significant active infection, cardiac disease, significant medical or psychiatric disease/condition that, in the opinion of the Investigator, would interfere with the interpretation of patient safety or study results or that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol – including (but not limited to):
    a. Bacterial sepsis, COVID-19, or other similarly severe infections (clinical assessment is the basis for exclusion of severe infections; if clinical suspicion, adequate testing should be performed to exclude severe infections).
    b. New York Heart Association > Grade 2 congestive heart failure within 6 months prior to randomization (see Protocol Section 12.2).
    c. Uncontrolled or significant cardiovascular disease
    d. Stroke within 6 months prior to randomization.
    e. Concurrent neurodegenerative disease.
    f. Dementia or significantly altered mental status.
    10. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome).
    11. Patients with a history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
    12. Patients with a history or known presence of tuberculosis.
    13. Pregnant and breastfeeding patients.
    14. Patients with a history or presence of human immunodeficiency virus (HIV) and/or active hepatitis B virus (HBV)/hepatitis C virus (HCV).
    15. Uncontrolled central nervous system (CNS) metastasis; patients with history of CNS metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to ICF signing and do not require corticosteroids for symptomatic management.
    16. Please refer to protocol for detailed exclusion criteria
    1. Pacientes tratados con dexametasona >2 mg/día o equivalente (es decir, 13 mg/día de prednisona) durante los 14 días anteriores a la aleatorización, a menos que sea necesario para tratar un acontecimiento adverso (AE).
    2. Pacientes tratados con radioterapia durante las 12 semanas anteriores al inicio del tratamiento del estudio y con quimioterapia citotóxica durante los 28 días (o 5 semividas de los compuestos administrados, si tienen más duración) anteriores al inicio del tratamiento del estudio.
    3. Pacientes con toxicidades persistentes de grado ≥2 (según NCI-CTCAE v5.0). Las toxicidades deben resolverse durante al menos 2 semanas a grado 1 o menos. Sin embargo, son aceptables la alopecia, la neuropatía y otras toxicidades persistentes que, a juicio del investigador, no constituyan un riesgo de seguridad.
    4. Pacientes que hayan recibido algún tratamiento previo con compuestos dirigidos a PD1, PD-L1, CTLA-4 o compuestos similares en los que podría haberse desarrollado una resistencia general contra las estrategias de vacunación terapéutica.
    5. Pacientes que hayan recibido trifluridina/tipiracilo (TAS-102) o regorafenib en el pasado.
    6. Pacientes con exposición previa a EO2401, EO2040 o EO4010, es decir, compuestos de vacunas terapéuticas que incluyen todos o algunos componentes de EO4010, el compuesto en investigación actual.
    7. Pacientes con los siguientes valores de laboratorio anómalos:
    a. Disminución del número de linfocitos de grado 2 (linfocitos <800 - 500/mm3; <0,8 - 0,5 x 109/L) o un grado peor.
    b. Hemoglobina <10 g/dl (6,2 mmol/L); la transfusión es aceptable para alcanzar el valor.
    c. Disminución del número absoluto de neutrófilos (<1,5 x109/L).
    d. Disminución del número de trombocitos (<75 × 109/L).
    e. Bilirrubina total >1,5 veces el límite superior de la normalidad (ULN; según los intervalos de referencia del laboratorio que hace la prueba); excepto participantes con síndrome de Gilbert que deben tener un nivel de bilirrubina total de <3,0 veces el ULN.
    f. Alanina aminotransferasa (ALT) >3 veces el ULN; si ha habido metástasis al hígado >5 veces el ULN.
    g. Aspartato aminotransferasa (AST) >3 veces el ULN; si ha habido metástasis al hígado >5 veces el ULN.
    h. Aumento de la creatinina sérica (>1,5 veces el ULN).
    i. Función tiroidea anómala según los niveles analíticos locales.
    8. Otra neoplasia maligna o neoplasia maligna previa con un intervalo sin enfermedad de menos de 3 años antes de la firma del FCI; excepto aquellos pacientes tratados con intervención quirúrgica y una probabilidad baja esperada de recurrencia, como cáncer de piel basocelular o epidermoide, o carcinoma in situ.
    9. Pacientes con infección activa clínicamente significativa, enfermedad cardíaca, enfermedad o condición médica o psiquiátrica significativa que, según el criterio del investigador, interferiría con la interpretación de la seguridad del paciente o los resultados del estudio o que impediría comprender u otorgar el consentimiento informado (es decir, solo los pacientes que pueden dar su consentimiento pueden participar en el estudio) y cumplir los requisitos del protocolo, incluidos (entre otros):
    a. Sepsis bacteriana, COVID-19 u otras infecciones graves similares (la evaluación clínica será la que servirá para excluir infecciones graves; si hay sospecha clínica, deben hacerse las pruebas adecuadas para excluir infecciones graves).
    b. Insuficiencia cardíaca congestiva de grado >2 según la New York Heart Association durante los 6 meses anteriores a la aleatorización (véase el apartado 12.2 del protocolo).
    c. Enfermedad cardiovascular importante o sin controlar, como:
    d. Ictus durante los 6 meses anteriores a la aleatorización.
    e. Enfermedad neurodegenerativa concomitante.
    f. Demencia o estado mental significativamente alterado.
    10. Pacientes con sospecha de trastorno autoinmunitario o autoinmunitario activo o antecedentes conocidos de una enfermedad neurológica autoinmunitaria (p. ej., síndrome de Guillain-Barré).
    11. Pacientes con antecedentes de trasplante de órgano sólido o trasplante alogénico de hemocitoblastos hematopoyéticos.
    12. Pacientes con antecedentes o presencia conocida de tuberculosis.
    13. Pacientes embarazadas o en periodo de lactancia.
    14. Pacientes con antecedentes o presencia del virus de la inmunodeficiencia humana (VIH) o virus de la hepatitis B (VHB) / virus de la hepatitis C (VHC) activos.
    15. Metástasis no controlada del sistema nervioso central (SNC); los pacientes con antecedentes de metástasis en el SNC pueden participar siempre y cuando la enfermedad del SNC haya permanecido estable desde el punto de vista radiográfico y neurológico durante al menos 6 semanas antes de la firma del FCI y no requieran corticoesteroides (ninguna dosis; en concreto para la enfermedad del SNC) para el tratamiento sintomático.
    16. Consulte el protocolo para conocer los criterios de exclusión detallados
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability of EO4010 in combination with nivolumab by a descriptive medical assessment of the combined profile of incidences of adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), deaths, reasons for treatment discontinuation/delays, and laboratory abnormalities using the NCI-CTCAE v5.0 grading system.
    Seguridad y tolerabilidad de EO4010 en combinación con nivolumab mediante una evaluación médica descriptiva del perfil combinado de incidencias de acontecimientos adversos (AEs), AEs emergentes del tratamiento (TEAEs), AEs graves (SAEs), muertes, motivos de interrupción/retraso del tratamiento y anomalías de laboratorio utilizando el sistema de clasificación NCI-CTCAE v5.0.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Continuous during study treatment and until Vd30 and Vd100.
    Continua durante el tratamiento del estudio y hasta Vd30 y Vd100.
    E.5.2Secondary end point(s)
    1. Percentage of patients with shown immunogenicity (expansion of specific T cells comparing samples taken at baseline versus on treatment in an individual patient determining if the patient has a positive response to the immunization, or not) in relation to EO2317, EO2318, OMP10, OMP11, OMP12, and UCP2 that compose EO4010 by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot), and by intracellular cytokines staining, or multimers staining assays. Cross reactivities with the human TAAs FOXM1, BIRC5/survivin, UBE2C, CDC20, and KIF2C will also be evaluated by the same methods.
    2. The ORT, ECT, TR and RD as described in the RECIST 1.1 and iRECIST criteria.
    3. PFS as described by RECIST 1.1 and iRECIST criteria, defined as the time interval from the date of first study treatment administration to the date of progression (by RECIST 1.1 or iRECIST criteria), or death due to any cause, whichever is earlier. Patients without progression or death are to be censored at the time of the last tumor assessment. The PFS rate at 4 months as assessed from the PFS survival curve.
    4. OS defined as the time interval from the date of first study treatment administration to the date of death due to any cause. Patients alive will be censored at the date of the last documented follow-up.
    1. Porcentaje de pacientes con inmunogenia demostrada (aumento de linfocitos T específicos comparando muestras tomadas al inicio frente a las tomadas durante el tratamiento en un paciente individual determinando si este responde de manera positiva a la inmunización o no) en relación con EO2317, EO2318, OMP10, OMP11, OMP12, y UCP2 que componen EO4010 por ImmunoSpot ligado a enzimas (ELISpot) de interferón-gamma (IFN-γ) y por tinción de citocinas intracelulares o ensayos de tinción de multímeros. Las reactividades cruzadas con los AAT humanos BIRC5/survivina, FOXM1, UBE2C, CDC20 y KIF2C también se evaluarán mediante los mismos métodos.
    2. La TRO, la TCE, la TR y la DR tal como se describe en los criterios RECIST 1.1 e iRECIST.
    3. La PFS, tal como se describe en los criterios RECIST 1.1 e iRECIST, se define como el intervalo desde la fecha de la primera administración del tratamiento del estudio hasta la fecha de progresión (según los criterios RECIST 1.1 o iRECIST) o fallecimiento por cualquier causa, lo que ocurra primero. Los pacientes que no progresen ni fallezcan serán objeto de censura estadística en el momento de la última evaluación del tumor. La tasa de SSP a los 4 meses evaluada a partir de la curva de supervivencia de SSP.
    4. OS definida como el intervalo desde la fecha de la primera administración del tratamiento del estudio hasta la fecha del fallecimiento por cualquier causa. Los pacientes vivos serán objeto de censura estadística en la fecha del último seguimiento documentado.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please see above
    Véase más arriba
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity analyses.
    Análisis de inmunogenicidad.
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    non-comparative, three sequential cohorts
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    France
    Spain
    Germany
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Ultima visita ultimo paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months36
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 13
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 29
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 31
    F.4.2.2In the whole clinical trial 42
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After participation in the trial, patients will be treated with the current standard therapy.
    Tras la participación en el ensayo, los pacientes serán tratados con la terapia estándar actual.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-08-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-24
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 06 23:17:44 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA