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    Summary
    EudraCT Number:2018-001973-25
    Sponsor's Protocol Code Number:MK-7339-001/ENGOT-ov43
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-11-08
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2018-001973-25
    A.3Full title of the trial
    A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First- Line Treatment of BRCA non-mutated Advanced Epithelial Ovarian Cancer (EOC) (EOC)(KEYLYNK-001 / ENGOT-ov43 / GOG-3036)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    First-line chemotherapy plus pembrolizumab and olaparib for BRCA non-mutated advanced EOC
    A.3.2Name or abbreviated title of the trial where available
    First-line chemotherapy plus pembrolizumab and olaparib for BRCA non-mutated advanced EOC
    A.4.1Sponsor's protocol code numberMK-7339-001/ENGOT-ov43
    A.5.4Other Identifiers
    Name:ENGOTNumber:ENGOT-ov43
    Name:KEYLINKNumber:KEYLYNK-001
    Name:Gynecologic Oncology GroupNumber:GOG-3036
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.1.3.4CountryUnited States
    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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 namePEMBROLIZUMAB
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form 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 INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Yes
    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.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 KEYTRUDA (pembrolizumab, MK-3475)
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    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.3.4Pharmaceutical form 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 INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Yes
    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.IMP: 3
    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 nameOlaparib
    D.3.2Product code AZD2281, KU-0059436
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOLAPARIB
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeMK-7339
    D.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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: 4
    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 nameOlaparib
    D.3.2Product code AZD2281, KU-0059436
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOLAPARIB
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeMK-7339
    D.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced epithelial ovarian cancer
    E.1.1.1Medical condition in easily understood language
    First line treatment of advanced ovarian cancer
    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 10033128
    E.1.2Term Ovarian 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
    1. To compare the progressionfree survival (PFS) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
    2. To compare overall survival (OS)
    E.2.2Secondary objectives of the trial
    1. To compare OS
    2. Compare the PFS as assessed by blinded independent central review
    according to RECIST 1.1
    3. Compare the PFS after next-line treatment (PFS2) following
    discontinuation of study treatment administration as determined by the
    investigator according to the local standard of clinical practice
    4. Evaluate the safety and tolerability of pembrolizumab administered
    with chemotherapy and olaparib maintenance
    5. Compare the GHS/QoL score using the EORTC, QLQC30 and
    abdominal/GI symptoms using the EORTC QLQOV28 abdominal/GI
    symptom scale
    6. Compare the time to first subsequent anti-cancer treatment , the time
    to second subsequent anti-cancer treatment, and the time to
    discontinuation of study treatment
    7. Compare the rate of locally determined pCR of pembrolizumab plus
    carboplatin/paclitaxel versus carboplatin/paclitaxel alone when
    administered as neoadjuvant therapy
    8. Compare the time without symptoms of disease progression or
    toxicity of treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Participant has histologically confirmed FIGO Stage III or Stage IV
    EOC (high-grade predominantly serous, endometrioid, (any grade),carcinosarcoma, mixed mullerian with highgrade serous component,
    clear cell, or low-grade serous OC), primary peritoneal cancer, or
    fallopian tube cancer
    2. Participant has just completed primary debulking surgery or is eligible
    for primary debulking surgery or is a potential candidate for interval
    debulking surgery.
    3. Participant is a candidate for carboplatin and paclitaxel chemotherapy,
    to be administered in the adjuvant or neoadjuvant setting
    4. Participant that is a candidate for neoadjuvant chemotherapy has a
    CA-125 (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio
    greater than or equal to 25
    5. Participant is able to provide a newly obtained core or excisional
    biopsy of a tumor lesion for prospective testing of BRCA1/2 and PD-L1
    status prior to randomization
    6. Participant is female and at least 18 years of age on the day of signing
    informed consent
    7. Participant has an Eastern Cooperative Oncology Group (ECOG)
    performance status of 0 or 1, as assessed within 7 days prior to initiating
    chemotherapy in the Lead-in Period and within 3 days prior to Day 1 of
    Cycle 1.
    8. A female participant is eligible to participate if she is not pregnant or
    breastfeeding, and at least 1 of the following conditions applies:
    •Is not a woman of childbearing potential (WOCBP)
    OR
    •Is a WOCBP and using a contraceptive method that is highly effective
    (with a failure rate of <1% per year), with low user dependency, or be
    abstinent from heterosexual intercourse as their preferred and usual
    lifestyle (abstinent on a long-term and persistent basis), during the
    Treatment Period and for at least 120 days following the last dose of
    pembrolizumab (or pembrolizumab placebo) and bevacizumab (if
    administered), at least 180 days following the last dose of olaparib (or
    olaparib placebo), and at least 210 days following the last dose of
    chemotherapy and agrees not to donate eggs (ova, oocytes) to others or
    freeze/store for her own use for the purpose of reproduction during this
    period. The investigator should evaluate the potential for contraceptive
    method failure (ie, noncompliance, recently initiated) in relationship to
    the first dose of study treatment.
    • A WOCBP must have a negative highly sensitive pregnancy test (urine
    or serum as required by local regulations) within either 24 hours (urine)
    or 72 hours (serum) before the first dose of study treatment.
    • If a urine test cannot be confirmed as negative (eg, an ambiguous
    result), a serum pregnancy test is required. In such cases, the
    participant must be excluded from participation if the serum pregnancy
    result is positive.
    • The investigator is responsible for review of medical history, menstrual
    history, and recent sexual activity to decrease the risk for inclusion of a
    woman with an early undetected pregnancy.
    • Contraceptive use by women should be consistent with local
    regulations regarding the methods of contraception for those
    participating in clinical studies. If the contraception requirements in the
    local label for any of the study interventions is more stringent than the
    requirements above, the local label requirements are to be followed.
    9. The participant (or legally acceptable representative if applicable)
    provides written informed consent for the study. The participant may
    also provide consent for future biomedical research; however, the
    participant may participate in the main study without participating in
    future biomedical research
    10. Participant has adequate organ function; all screening laboratory
    tests should be performed within 7 days prior to starting chemotherapy
    in the Lead-in Period.
    E.4Principal exclusion criteria
    1.Participant has mucinous, germ cell, or borderline tumor of the ovary
    2.Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
    3.Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
    4.Participant either has myelodysplastic syndrome (MSD)/acute myeloid leukemia (AML)or has features suggestive of MDS/AML
    5.Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years
    6.Participant has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the Lead-in Period
    7.Participant has known active central nervous system metastases and/or carcinomatous meningitis
    8.Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7days prior to randomization
    9.Participant has an active autoimmune disease that has required systemic treatment in the past 2years
    10.Participant has a known history of active tuberculosis
    11.Participant has an active infection requiring systemic therapy
    12. Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator
    13. Participant has received colony-stimulating factors within 4 weeks (28days) prior to receiving chemotherapy during the Lead-in Period.
    14. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
    15. Participant has had surgery <6 months prior to screening to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer
    16. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study
    17. Participant has a known history of human immunodeficiency virus (HIV) infection.
    18. Participant has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsag] reactive) or known active hepatitis C virus infection.
    19. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption
    20. Participant has uncontrolled hypertension.
    21. Participant has current, clinically relevant bowel obstruction, abdominal fistula or gastrointestinal perforation, related to underlying EOC
    22.Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization
    23.A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to Day1 od Cycle1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study.
    24.Participant has received prior treatment for any stage of OC
    25.Participant has received prior therapy with an anti-PD-1, anti-PD-L1,or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
    26.Participant has received prior therapy with either olaparib or any other PARP inhibitor
    27.Is a participant for whom intraperitoneal chemotherapy is planned or has been administered as first-line therapy
    28.Participant has received a live vaccine within 30days prior to the first dose of study treatment on Day 1 of Cycle 1
    29.Participant has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their excipients
    30.Participant is currently receiving either strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 that cannot be discontinued prior to starting olaparib or olaparib placebo and for the duration of the study
    31.Participant is currently participating/has participated in a study of an investigational agent or has used an investigational device within 4weeks (28days) of starting chemotherapy in Lead-in Period
    32.Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator, or participant has congenital long QT syndrome
    33.Participant has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation
    34.Participant either had major surgery within 2weeks of randomization or has not recovered from any effects of any major surgery
    35.Participant, in the judgement of the investigator, is unlikely to comply with requirements of the study
    E.5 End points
    E.5.1Primary end point(s)
    1) Progression-free survival (PFS) based on RECIST 1.1 as assessed by investigator in participants with PD-L1 positive tumors (CPS ≥10)
    • PFS per RECIST 1.1 assessed by investigator in all participants.
    E.5.1.1Timepoint(s) of evaluation of this end point
    IA1: PFS and OS analysis around 42 months after the first participant
    is randomized, when ~257 PFS events are observed in participants with
    CPS ≥10, and ~ 513 PFS events have been observed in all participants
    for Arm 1 versus Arm 3 comparison.
    • IA2: PFS and OS analysis around 55 months after the first participant
    is randomized, when ~306 PFS events are observed in participants with
    CPS ≥10, and ~ 611 PFS events have been observed in all participants
    for Arm 1 versus Arm 3 comparison
    E.5.2Secondary end point(s)
    • Overall survival (OS) in all participants
    • PFS based on RECIST 1.1 as assessed by BICR
    • PFS after next-line treatment (PFS2)
    • Safety and tolerability of the 3 treatment groups
    E.5.2.1Timepoint(s) of evaluation of this end point
    • IA1: PFS and OS analysis around 42 months after the first participant
    is randomized, when ~257 PFS events are observed in participants with
    CPS ≥10, and ~ 513 PFS events have been observed in all participants
    for Arm 1 versus Arm 3 comparison.
    • IA2: PFS and OS analysis around 55 months after the first participant
    is randomized, when ~306 PFS events are observed in participants with
    CPS ≥10, and ~ 611 PFS events have been observed in all participants
    for Arm 1 versus Arm 3 comparison.
    • FA: OS analysis around 70 months after the first participant is
    randomized, when ~445 OS events are observed in all participants for
    Arm 1 versus Arm 3 comparison
    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 Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA70
    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
    Australia
    Belgium
    Brazil
    Canada
    Chile
    Colombia
    Czechia
    France
    Germany
    Hungary
    Ireland
    Israel
    Italy
    Japan
    Korea, Republic of
    New Zealand
    Poland
    Russian Federation
    South Africa
    Spain
    Taiwan
    Turkey
    Ukraine
    United Kingdom
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    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: 815
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 470
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 650
    F.4.2.2In the whole clinical trial 1284
    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)
    If a participant has confirmed radiographic progression (iCPD) as per the protocol study treatment should be discontinued; however, if the participant is achieving a clinically meaningful benefit, an exception to continue study treatment may be considered following consultation with the Sponsor
    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 Decision2019-01-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-06
    P. End of Trial
    P.End of Trial StatusOngoing
    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
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