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    Summary
    EudraCT Number:2018-003824-35
    Sponsor's Protocol Code Number:MK-7902-006
    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:2019-03-06
    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 number2018-003824-35
    A.3Full title of the trial
    A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) with or without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants with Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab with or without Lenvatinib in Participants with NSCLC
    A.3.2Name or abbreviated title of the trial where available
    LEAP-006
    A.4.1Sponsor's protocol code numberMK-7902-006
    A.5.4Other Identifiers
    Name:IND numberNumber:140221
    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.4.1Name of organisation providing supportEisai Limited
    B.4.2CountryUnited Kingdom
    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 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.3.1Product 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 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 nameLenvatinib
    D.3.2Product code E7080
    D.3.4Pharmaceutical form Capsule, hard
    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 INNLENVATINIB MESILATE
    D.3.9.1CAS number 857890-39-2
    D.3.9.2Current sponsor codeMK-7902
    D.3.9.3Other descriptive nameLENVATINIB MESILATE
    D.3.9.4EV Substance CodeSUB72971
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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: 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 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: 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 nameLenvatinib
    D.3.2Product code E7080
    D.3.4Pharmaceutical form Capsule, hard
    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 INNLENVATINIB MESILATE
    D.3.9.1CAS number 857890-39-2
    D.3.9.2Current sponsor codeMK-7902
    D.3.9.3Other descriptive nameLENVATINIB MESILATE
    D.3.9.4EV Substance CodeSUB72971
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 placeboCapsule, hard
    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
    Metastatic Nonsquamous Non-small Cell Lung Cancer
    E.1.1.1Medical condition in easily understood language
    Metastatic Nonsquamous Non-small Cell Lung Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung 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 10079440
    E.1.2Term Non-squamous non-small cell lung 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
    Part 1: To evaluate the safety and tolerability of treatment with lenvatinib + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1 as defined in Section 4.2.1.1.3) for lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab. - Hypothesis (H1): The combination of lenvatinib +platinum doublet chemotherapy + pembrolizumab prolongs PFS per RECIST 1.1 by BICR compared to matching placebo + platinum doublet chemotherapy +pembrolizumab.
    Part 2: To compare OS for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy +pembrolizumab.
    E.2.2Secondary objectives of the trial
    Part 2: To compare objective response rate (ORR) as assessed by BICR according to RECIST 1.1 for the combinations of lenvatinib + platinum doublet chemotherapy+pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare duration of response (DOR) per RECIST 1.1 by BICR for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare the safety and tolerability for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare the mean change from baseline in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participant must:
    1. Have a histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC], version 8 or current version) nonsquamous NSCLC.
    2. Have confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as
    primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a KRAS mutation).
    3. Have measurable disease per RECIST 1.1. .
    4. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Formalin fixed specimens after the participant has been diagnosed with metastatic disease are preferred. Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy are permitted if recent biopsy is not feasible.
    5. Be male or female ≥18 years of age inclusive, at the time of signing the informed consent form (ICF).
    6. Have a life expectancy of at least 3 months.
    7. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
    8. Male participants are eligible to participate if they agree to the
    following during the intervention period and for at least 30 days after
    the last dose of lenvatinib/matching placebo and up to 180 days after
    the last dose of chemotherapeutic agents:
    • Refrain from donating sperm
    PLUS either:
    • Be abstinent from heterosexual intercourse as their preferred and
    usual lifestyle (abstinent on a long term and persistent basis) and agree
    to remain abstinent
    OR
    • Must agree to use contraception unless confirmed to be azoospermic
    (vasectomized or secondary to medical cause ) as detailed below:
    - Agree to use a male condom plus partner use of an additional
    contraceptive method when having penile-vaginal intercourse with a
    WOCBP who is not
    currently pregnant. Note: Men with a pregnant or breastfeeding partner
    must agree to remain abstinent from penile-vaginal intercourse or use a
    male condom during each episode of penile-vaginal penetration.
    9. A female participant is eligible to participate if she is not pregnant or
    breastfeeding, and at least one of the following conditions applies:
    - Is not a 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
    intervention period and for at least 120 days post pembrolizumab and 30
    days post-lenvatinib/matching placebo, and up to 180 days post last
    dose of chemotherapeutic agents, whichever occurs last. The investigator should evaluate the potential
    for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
    - A WOCBP must have a negative highly sensitive pregnancy test (urine
    or serum as required by local regulations) within 24 hours before the
    first dose of study intervention.
    - 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.
    10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
    11. Have adequate organ function as indicated by the laboratory values.
    Specimens must be collected and reviewed within 10 days prior to the first dose of study intervention.
    12. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization.
    E.4Principal exclusion criteria
    If Participant:
    1. Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 4 weeks by repeat imaging [the repeat imaging must be performed during the screening period]), clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
    2. Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
    3. Radiographic evidence of intratumoral caviations, encasement, or
    invasion of a major blood vessel. Additionally, the degree of proximity to
    major blood vessels should be considered because for exclusion because
    of the potential risk of severe hemorrhage associated with tumor
    shrinkage/necrosis after lenvatinib therapy. (In the chest, major blood
    vessels include the main pulmonary artery, the left and right pulmonary
    arteries, the 4 major pulmonary veins, the superior or inferior vena cava,
    and the aorta).
    4. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
    5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
    Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
    6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
    7. Has had an allogeneic tissue/solid organ transplant.
    8. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
    9. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as HCV
    RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection. No testing for Hepatitis B or Hepatitis C is required unless mandated by the
    local health authority.
    10. Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
    11. Has active hemoptysis (at least 0.5 tsp of bright red blood) within 2 weeks prior to the first dose of study intervention.
    12. Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
    13. Has a known history of active tuberculosis.
    14. Has an active infection requiring systemic therapy.
    15. Has had major surgery within 3 weeks prior to first dose of study
    interventions.
    16. Has known psychiatric or substance abuse disorders that would interfere with the participant’s cooperation to meet with the requirements of the study.
    17. Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed.
    18. A WOCBP who has a positive urine pregnancy test within 24 hours
    prior to randomization or treatment allocation. If the urine test is
    positive or cannot be confirmed as negative, a serum pregnancy test will
    be required.
    19. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal
    fistula.
    20. Has received prior systemic chemotherapy or other targeted or
    biological antineoplastic therapy for their metastatic NSCLC.
    21. Has received prior treatment with pembrolizumab or any other anti
    PD 1, anti PD L1, anti PD L2 agent, with lenvatinib or any other RTKi, or
    with an agent directed to another stimulatory or co inhibitory T cell
    receptor (eg, CTLA-4, OX-40, CD137, GITR).
    22. Has received radiotherapy within 14 days prior to the first dose of
    study intervention or received lung radiation therapy of >30 Gy within 6
    months prior to the first dose of study intervention.
    23. Has received systemic steroid therapy (in doses exceeding 10 mg
    daily of prednisone equivalent) within 7 days prior to the first dose of
    study intervention.
    24. Has received a live vaccine within 30 days prior to the first dose of
    study intervention.
    E.5 End points
    E.5.1Primary end point(s)
    1. Part 1: Number of Participants with a Dose-limiting Toxicity
    2.Part 1: Number of Participants with One or More Adverse Events
    3.Part 2: Progression-free Survival (PFS) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ
    4. Part 2: Overall Survival (OS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Cycle 1; each cycle is 21 days (up to 21 days)
    2. Through 90 days post last dose of study treatment (Up to approximately 27 months)
    3. Up to approximately 24 months
    4. Up to approximately 60 months
    E.5.2Secondary end point(s)
    1. Part 2: Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ
    2. Part 2; Duration of Response (DOR) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ
    3. Part 2: Number of Participants with One or More Adverse Events
    4. Part 2: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event
    5. Part 2: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 [EORTC QLQ-C30] Global Health Status/Quality of Life (QoL)(EORTC QLQ-C30 Items 29 and 30); Cough (EORTC QLQ-Lung Cancer Module [LC13] Item 31); Chest Pain (EORTC QLQ-LC13 Item 40); Dyspnea (EORTC QLQ-C30 Item 8); and Physical Functioning (EORTC QLQ-C30 Items 1-5) Combined Score
    6. Part 2: Time to True Deterioration as Assessed by Change from Baseline in Global Health Status/QoL (EORTC QLQ-C30 Items 29 and 30), Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), Dyspnea (EORTC QLQ-C30 Item 8), and Physical Functioning (EORTC QLQ-C30 Items 1-5) Combined Score
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 24 months
    2. Up to approximately 24 months
    3. Up to approximately 24 months
    4. Up to approximately 24 months
    5. Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
    6. Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    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 No
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA66
    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
    Argentina
    Australia
    Canada
    Chile
    China
    France
    Germany
    Israel
    Japan
    Korea, Republic of
    New Zealand
    Poland
    Russian Federation
    Spain
    Turkey
    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
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    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: 430
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 285
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 372
    F.4.2.2In the whole clinical trial 714
    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)
    None
    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 Decision2019-03-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-14
    P. End of Trial
    P.End of Trial StatusOngoing
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