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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42782   clinical trials with a EudraCT protocol, of which   7047   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:2019-003396-19
    Sponsor's Protocol Code Number:EOADR1-19
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-03-31
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2019-003396-19
    A.3Full title of the trial
    A phase 1/2 trial of EO2401, a novel microbial-derived peptide therapeutic vaccine, in combination with PD-1 check point blockade, for treatment of
    patients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Early Phase Clinical Trial to investigate EO2401, a Novel Cancer Vaccine Therapy, with an Immune-Checkpoint Blocker, in Patients with unresectable, previously treated and previously untreated, locally advanced or metastatic adrenocortical carcinoma or malignant pheochromocytoma/paraganglioma, a Certain Form of adrenals cancer
    A.4.1Sponsor's protocol code numberEOADR1-19
    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
    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
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationENTEROME
    B.5.2Functional name of contact pointJean-Michel Paillarse
    B.5.3 Address:
    B.5.3.1Street Address94/96 avenue Ledru-Rollin
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75001
    B.5.3.4CountryFrance
    B.5.4Telephone number+33185 76 10 62
    B.5.6E-mailjmpaillarse@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.3.2Product code EO2401
    D.3.4Pharmaceutical form Emulsion for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeEO2316
    D.3.9.3Other descriptive nameEO2316
    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.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeEO2317
    D.3.9.3Other descriptive nameEO2317
    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.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeEO2318
    D.3.9.3Other descriptive nameEO2318
    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.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeUCP2
    D.3.9.3Other descriptive nameUCP2
    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.3.9.1CAS number 190396-06-6
    D.3.9.3Other descriptive nameMONTANIDE ISA51
    D.3.9.4EV Substance CodeSUB33722
    D.3.10 Strength
    D.3.10.1Concentration unit µl/ml microlitre(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 (10mg/mL)
    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.3.4Pharmaceutical 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.3.9.2Current sponsor codeN/A
    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
    - locally advanced or metastatic adrenocortical carcinoma (ACC)
    - malignant pheochromocytoma/paraganglioma (MPP)
    E.1.1.1Medical condition in easily understood language
    - locally advanced or metastatic adrenocortical carcinoma (ACC)
    - malignant pheochromocytoma/paraganglioma (MPP)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10001388
    E.1.2Term Adrenocortical 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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10034876
    E.1.2Term Pheochromocytoma
    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 10075444
    E.1.2Term Malignant paraganglioma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    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
    EO2401 in combination with nivolumab in patients with unresectable,
    previously treated, and previously untreated, locally advanced or
    metastatic ACC, and progressive MPP.
    E.2.2Secondary objectives of the trial
    The key secondary objectives of the trial are:
    - immunogenicity in relation to T cells of EO2316, EO2317, EO2318, and
    UCP2 that compose EO2401; T cell cross-reactivity with the human TAAs
    IL13Rα2, FOXM1, and BIRC5/surviving will also be evaluated,
    The other secondary objectives of the trial are:
    - objective response rate (ORR), time to response and duration of response (DOR), and
    - progression-free survival (PFS) and overall survival (OS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. For inclusion in Cohort 1 patients should have adrenocortical
    carcinoma, or malignant pheochromocytoma/paraganglioma, as defined below for Cohorts 2A and 3A.
    Note, for sites in Denmark, Sweden and USA, no recruitment to the trial will start before an IDMC recommendation, and Sponsor decision, to open Cohorts 2 and 3 as outlined in Sections 4.2.1 and 4.2.2 of the protocol, i.e. inclusion criterion #1 is not applicable for patients recruited at sites in Denmark, Sweden and USA.
    2. For inclusion in Cohorts 2A and 2B patients should have histologically
    confirmed (at primary diagnosis) unresectable locally advanced or
    metastatic (ENSAT/AJCC] stage 3 = tumor has spread into nearby
    tissues or lymph nodes, or stage 4 = metastatic disease) adrenocortical
    carcinoma.
    a. In addition, for inclusion in Cohort 2 A patients should also have
    received treatment with at least one line, but not more than two prior
    lines, of systemic therapy for established locally advanced or metastatic
    disease (i.e. non-adjuvant therapy)
    b. In addition, for inclusion in Cohort 2B patients should not have
    received prior systemic therapy for established locally advanced or
    metastatic disease (i.e. non-adjuvant therapy).
    Note, for both Cohorts 2A and 2B, adjuvant therapy (including mitotane
    with or without chemotherapy) for patients after complete response to
    local therapy (e.g. resection) should not be counted in the definitions
    above for line of therapy for established disease. Patients who have
    received mitotane as adjuvant therapy can continue mitotane during
    study therapy provided tumor recurrence has been demonstrated at
    mitotane therapeutic plasma level (> 14 mg/L) or at maximum
    individual tolerated dose.
    3. For inclusion in Cohorts 3A and 3B patients should have histologically
    confirmed (at primary diagnosis) unresectable malignant (defined as
    metastatic disease, i.e. presence of chromaffin tissue in non-chromaffin
    organs pheochromocytoma/paraganglioma, and RECIST defined
    progression should have been documented during a maximum of an
    18months period.
    a. In addition, for inclusion in Cohort 3A patients should also have
    received treatment with at least two prior lines of systemic therapy if
    the patients are eligible for radionuclide therapy, and at least one prior
    line of systemic therapy if the patients are not eligible for radionuclide
    therapy.
    b. In addition, for inclusion in Cohort 3B patients should not have
    received prior systemic therapy for their malignant pheochromocytoma/paraganglioma.
    4. Patients with an age ≥ 18 years old.
    5. Patients who are human leukocyte antigen (HLA)-A2 positive.
    6. Patients with an Eastern Cooperative Oncology Group (ECOG)
    performance status ≤ 2 (see Section 12.2 [39]).
    7. Patients with a life expectancy > 4 months as judged by their treating
    physician.
    8. Patients with at least one measurable lesion according to RECIST 1.1
    (see Section 12.1).
    9. Males or non-pregnant, non-lactating, females who are:
    a) female, post-menopausal (serum follicle-stimulating hormone (FSH) level > 40 mIU/mL),
    b) female and male, surgically sterile (e.g. bilaterally blocked or removed
    fallopian tubes, vas deferens),
    c) female of childbearing potential with a negative highly sensitive
    serum pregnancy test within 72 hours prior to first administration of
    study treatment and use of a highly effective contraception from signing
    the Informed Consent Form (ICF) through 5 months after the last study
    treatment dose administered; note, the male partner should in addition
    to the use of highly effective contraception by the female patient also
    use condoms,
    d) male patient with female partners of childbearing potential must use
    condoms from signing the ICF through 5 months after the last study
    treatment dose administered; in addition, male patients must ensure
    that their partners of childbearing potential also use highly effective
    contraception.
    Highly effective contraception include:
    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, intrauterine device, and
    iii) 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).
    10. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
    11. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures. Note, a 2-stage consent procedure is going to be used in the trial (see Section 4.2); the first minimized consent related to the procedure of HLA-testing, and the second to all other trial details and procedures.
    E.4Principal exclusion criteria
    1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e.
    13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14
    days before the first EO2401 administration, unless required to treat an
    adverse event. Note, inhaled steroids and adrenal replacement steroid
    doses > 13 mg daily prednisone equivalents are permitted. Thus,
    patients needing hydrocortisone replacement therapy due to prior or
    ongoing mitotane therapy can receive hydrocortisone doses > 53
    mg/day, i.e. also in the normally used range of 60-80 mg/day, and still
    be included in the trial.
    2. Patients with prior treatment with compounds targeting PD-1, PD-L1,
    CTLA-4, or similar compounds where general resistance against
    therapeutic vaccination approaches might have developed (e.g. defects
    to the cellular antigen processing/presentation machinery, including
    mutations in Janus kinas [JAK] 1, JAK2, and β-2-microglobulin [B2M])
    allowing tumor cells to avoid recognition and attack by immune cells.
    3. Patients with prior exposure to EO2401, e.g. patients treated in
    Cohorts 2B or 3B of the current trial cannot be re-enrolled for treatment
    also in Cohorts 2A or 3A.
    4. Patients treated with immunotherapy (meaning immunostimulatory or
    immunosuppressive therapy; beside excluded, or allowed, compounds
    per other inclusion/exclusion criteria specifications), radionuclide
    therapy, radiotherapy, cytoreductive therapy, or received treatment with
    any other investigational agent within 28 days before the first EO2401
    administration. Note, for patients with ACC continued treatment with
    mitotane during this trail is allowed provided tumor progression on this
    therapy has been demonstrated under therapeutic plasma level (>
    14mg/L) or at maximum individual tolerated dose and mitotane plasma
    level monitoring is maintained during the trial (mitotane might have
    been given in the adjuvant and/or established disease settings as long
    as progression on this therapy before trial inclusion has been
    documented).
    For patients with MPP, concurrent therapy with somatostatin, and
    somatostatin analogues is allowed provided tumor progression on this
    therapy has been demonstrated; concurrent therapy with
    bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed.
    5. Patients with ACC with more than three organs involved by disease,
    combined with unresectable primary tumor.
    6. Patients with ACC and uncontrolled hormonal secretion (according to
    the judgement of the treating physician).
    7. Patients with MPP and uncontrolled blood pressure (according to the
    judgement of the treating physician).
    8. Patients with abnormal laboratory values according to the following
    list (note, lab ranges according to the performing laboratory's reference
    ranges):
    a. hemoglobin < 8 g/dL (9 mmol/L) i.e. anemia Grade 2 is acceptable if
    judged by the Investigator as not constituting a safety risk in the
    individual patient,
    b. white blood cell count decrease (< 3.0 × 109/L),
    c. absolute neutrophil count decrease (< 1.5 × 109/L),
    d. platelet count decrease (< 75 × 109/L),
    e. bilirubin > 1.5 x upper limit of normal (ULN) (note, benign hereditary
    hyperbilirubinemia, e.g. Gilbert's syndrome is permitted),
    f. alanine aminotransferase (ALT) > 3 x ULN; if disease metastatic to the
    liver > 5 x ULN,
    g. aspartate aminotransferase (AST) > 3 x ULN; if disease metastatic to
    the liver > 5 x ULN,
    h. serum creatinine increase (> 1.5 x ULN); however, if creatinine
    clearance (measured, or calculated according to the Cockcroft/Gault or
    the CKD-EPI equation) is > 40 mL/minute the patient can be enrolled,
    i. abnormal thyroid function per local laboratory levels (note, patients
    with hypothyroidism only requiring hormone replacement therapy are
    permitted to enroll, also patients with abnormal laboratory values
    judged by the treating physician as clinically non-relevant and related to
    mitotane treatment are allowed to enroll).
    9. Patients with persistent Grade 3 or 4 toxicities (according to
    NCICTCAE v5.0) after prior treatments; toxicities must be resolved since
    at least 2 weeks before study treatment start to Grade 1 or less.
    However, alopecia or other persisting toxicities Grade ≤ 2 not
    constituting a safety risk based on Investigator's judgment are
    acceptable.
    10. 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 (of any dose; for the CNS
    disease specifically) for symptomatic management.
    11. 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, i.e. patients with
    adequately treated basal cell or squamous cell skin cancer, or carcinoma
    in situ are eligible.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint regarding safety and tolerability of EO2401 in
    combination with nivolumab is a descriptive medical assessment of the
    combined profile of incidences of adverse events (AEs), treatmentemergent
    AEs (TEAEs), serious AEs (SAEs), deaths, reasons for treatment discontinuation/delays, and laboratory abnormalities using the NCI-CTCAE v5.0 grading system.
    E.5.1.1Timepoint(s) of evaluation of this end point
    AEs will be monitored throughout the study. AEs are collected from the date of the patient's signing the ICF until 30 days after the final administration of study drug. SAEs with a plausible causal relationship to study drug will be reported from the date of the patient's signing the ICF until indefinitely (regardless of time elapse from the final study drug administration). An AE causally not related to study drug will be monitored (followed-up) until resolution, stabilization, or end of the clinical trial. Clinically relevant laboratory abnormalities will be followed up until they return to normal or become stabilized (permanent condition). Any AE with a plausible causal relationship to study drug as well as all SAEs will be followed up until the event has resolved or
    stabilized.
    E.5.2Secondary end point(s)
    The key secondary endpoints of the trial are:
    • Percentage of patients with shown immunogenicity (expansion of
    specific T cells comparing samples taken at baseline versus on treatment
    n an individual patient determining if the patient has a positive response
    to the immunization, or not) in relation to EO2316, EO2317, EO2318, and
    UCP2 that compose EO2401 by interferon-gamma (IFN-γ) enzyme-linked
    immunospot (ELISpot), and if needed by intracellular cytokines staining,
    or multimers staining assays. Cross reactivities with the human TAAs
    IL13Rα2, FOXM1, and BIRC5/survivin will also be evaluated by the same
    methods.
    The other secondary endpoints of the trial are:
    • ORR, time to response and DOR as described by RECIST 1.1 and iRECIST criteria.
    • 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.
    • 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.
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Percentage of patients with shown immunogenicity is evaluated on
    Week 1, 5 , 7 , 11, 15 and 19, then every 4 weeks of treatment onwards.
    Post treatment is evaluated on Day 30 and every 8 weeks before disease
    progression
    • Objective Response Rate (ORR) and Duration of Response (DOR) as
    described by RECIST 1.1 and iRECIST criteria
    • 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.
    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
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    A phase Ib/II trial but another trial is the Fist in Human
    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
    The trial is a 5-cohort study
    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.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 EEA8
    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
    Denmark
    France
    Germany
    Italy
    Netherlands
    Spain
    Sweden
    United States
    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
    Last Visit Last Patient (LVLP)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    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: 47
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 25
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 64
    F.4.2.2In the whole clinical trial 72
    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)
    The investigator will ensure that patients receive appropriate standard of care to treat the condition under the study
    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 Decision2020-03-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-26
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA