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    Summary
    EudraCT Number:2015-005696-24
    Sponsor's Protocol Code Number:MS200095-0022
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-25
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-005696-24
    A.3Full title of the trial
    A Phase II single-arm trial to investigate tepotinib in advanced (locally advanced or metastatic) non-small cell lung cancer with MET exon 14 (METex14) skipping alterations or MET amplification (VISION)
    Sperimentazione di fase II a braccio singolo per la valutazione di tepotinib nel carcinoma polmonare non a piccole cellule avanzato (localmente avanzato o metastatico) con alterazioni associate a skipping dell’esone 14 di MET (METex14) o amplificazione di MET (VISION)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Tepotinib Phase II study in advanced lung cancer harboring MET exon 14 (METex14) skipping alterations and MET amplification
    Studio di fase II di Tepotinib nel carcinoma polmonare avanzato con alterazioni associate a skipping dell’esone 14 di MET (METex14) o amplificazione di MET
    A.3.2Name or abbreviated title of the trial where available
    Tepotinib Phase II study in lung adenocarcinoma harbouring MET exon 14 (METex14) skipping alteration
    Studio di fase 2 su Tepotinib nell'adenocarcinoma polmonare con alterazioni associate a skipping del
    A.4.1Sponsor's protocol code numberMS200095-0022
    A.5.4Other Identifiers
    Name:AcronymNumber:VISION
    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 KGAA
    B.1.3.4CountryGermany
    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 KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck KGaA
    B.5.2Functional name of contact pointCommunication Center
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Str. 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.3.4CountryGermany
    B.5.4Telephone number496151725200
    B.5.5Fax number496151722000
    B.5.6E-mailservice@merckgroup.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 nametepotinib
    D.3.2Product code MSC2156119J
    D.3.4Pharmaceutical form 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 INNtepotinib
    D.3.9.2Current sponsor codeMSC2156119J
    D.3.9.3Other descriptive nameMSC2156119J
    D.3.9.4EV Substance CodeSUB177092
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 nametepotinib
    D.3.2Product code MSC2156119J
    D.3.4Pharmaceutical form 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 INNtepotinib
    D.3.9.2Current sponsor codeMSC2156119J
    D.3.9.3Other descriptive nameMSC2156119J
    D.3.9.4EV Substance CodeSUB177092
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 nametepotinib
    D.3.2Product code [MSC2156119J]
    D.3.4Pharmaceutical form 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 INNTEPOTINIB
    D.3.9.2Current sponsor codeMSC2156119J
    D.3.9.4EV Substance CodeSUB189535
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced (stage IIIB/IV) non-small cell lung cancer with MET exon 14 (METex14) skipping alterations
    Carcinoma polmonare non a piccole cellule avanzato (stadio IIIB / IV) con alterazioni saltate di MET exon 14 (METex14)
    E.1.1.1Medical condition in easily understood language
    Lung cancer
    Tumore ai polmoni
    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 LLT
    E.1.2Classification code 10001165
    E.1.2Term Adenocarcinoma lung stage IV
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10001160
    E.1.2Term Adenocarcinoma lung
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10001164
    E.1.2Term Adenocarcinoma lung stage III
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    COHORT A (METex14 skipping alterations):
    To assess the efficacy of tepotinib in subj. with advanced NSCLC
    harboring the METex14 skipping alterations, as per objective response
    acc. to RECIST ver. 1.1, based on independent review in
    • - Subjects tested positive for METex14 skipping alterations, regardless
    of MET amplification status
    • -Subjects tested positive for METex14 skipping alterations based on
    liquid biopsy (LBx), regardless of MET amplification status
    • -Subjects tested positive for METex14 skipping alterations based on
    tumor biopsy (TBx), regardless of MET amplification status.
    COHORT B (MET amplification):
    • To assess the efficacy of tepotinib in subjects with advanced (Stage
    IIIB/IV) NSCLC, as per objective response accord. to RECIST Ver. 1.1,
    based on independent review in:
    •- Subj.tested positive for MET amplification in LBx, and negative for
    METex14 skipping alterations.
    COHORT A (alterazioni di salto METex14):
    Per valutare l'efficacia di tepotinib in subj. con NSCLC avanzato
    ospitare le alterazioni di salto METex14, come da risposta obiettiva
    acc. per RECIST ver. 1.1, sulla base di una revisione indipendente in
    • - Soggetti testati positivi per alterazioni saltate di METex14, indipendentemente
    dello stato di amplificazione MET
    • -Soggetti testati positivi per alterazioni di salto di METex14 basate su
    biopsia liquida (LBx), indipendentemente dallo stato di amplificazione del MET
    • -Soggetti testati positivi per alterazioni di salto di METex14 basate su
    biopsia tumorale (TBx), indipendentemente dallo stato di amplificazione del MET.
    COHORT B (amplificazione MET):
    • Valutare l'efficacia di tepotinib in soggetti con avanzato (stadio
    IIIB / IV) NSCLC, come da accordo di risposta obiettiva. per RECIST Ver. 1.1,
    basato su una revisione indipendente in:
    • - Subj.test positivo per l'amplificazione MET in LBx e negativo per
    Alterazioni di salto METex14.
    E.2.2Secondary objectives of the trial
    E.2.2 Obiettivi secondari:
    COHORT A and B:
    To further assess the efficacy of tepotinib
    - To assess tolerability and safety of tepotinib
    - To assess PK of tepotinib and its metabolite(s)
    - To assess Health-Related Quality of Life (HRQoL)
    Exploratory Objectives
    -To explore a possible link between biomarkers of c-Met pathway
    activation, other relevant oncogenic pathways in plasma, serum and
    tumor tissue, and the activity of tepotinib
    - To explore the QT/QTc interval concentration relationship based on
    Cycle 1, Day 1 and Cycle 2, Day 1 data
    - To investigate the exposure-response relationship
    E.2.2 Obiettivi secondari:
    COH0RT A e B:
    Per valutare ulteriormente l'efficacia di tepotinib
    - Valutare la tollerabilità e la sicurezza di tepotinib
    - Valutare la PK di tepotinib e il suo / i suo / i metabolita / i
    - Valutare la qualità della vita correlata alla salute (HRQoL)
    Obiettivi esplorativi
    -Per esplorare un possibile collegamento tra biomarcatori del percorso c-Met
    attivazione, altre vie oncogeniche rilevanti nel plasma, nel siero e
    tessuto tumorale e l'attività di tepotinib
    - Per esplorare la relazione di concentrazione dell'intervallo QT / QTc in base a
    Ciclo 1, giorno 1 e ciclo 2, giorno 1 dati
    - Indagare la relazione esposizione-risposta
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Pharmacogenetics
    Version: V5.0
    Date: 10/05/2018
    Title: Pharmacogenetics
    Objectives: the DNA extracted for genetic variant analysis may be explored for potential genes involved in the PK, pharmacodynamics, efficacy and safety of tepotinib. Biomarkers of c-Met and other pathway activations, such as but not limited to phospho-c-Met, HGF levels, c-Met genetic mutations, and their potential correlation with prognosis and activity of tepotinib will be assessed. This consists of analyzing the type and the level of biomarkers alteration in serum or tumor tissue and evaluating their association with clinical endpoints. Blood samples for PGx will be evaluated to assess genetic variations of genes. Pharmacogenetics testing might include assessment of genetic polymorphisms responsible for drug metabolism and transport genes and may also be used for assessing polymorphisms linked to Caucasian or Asian descent. Other biomarkers and technologies may be included, the scientific relevance of which emerges at the time of the planned analysis for subjects included in the trial.

    Farmacogenetica
    Versione: V5.0
    Data: 10/05/2018
    Titolo: Farmacogenetica
    Obiettivi: il DNA estratto per l'analisi delle varianti genetiche può essere esplorato per potenziali geni coinvolti nel PK, farmacodinamica, efficacia e sicurezza di tepotinib. Biomarcatori di c-Met e altre attivazioni di pathway, come ma non limitato a phospho-c-Met, Livelli di HGF, mutazioni genetiche c-Met e loro potenziale correlazione con saranno valutate la prognosi e l'attività di tepotinib. Questo consiste di analizzare il tipo e il livello di alterazione dei biomarcatori nel siero o nel tessuto tumorale e valutarne l'associazione con gli endpoint clinici. Saranno valutati campioni di sangue per PGx per valutare le variazioni genetiche dei geni. I test di farmacogenetica potrebbero includere la valutazione dei polimorfismi genetici responsabili del metabolismo dei farmaci e dei geni di trasporto e possono anche essere utilizzati per valutare i polimorfismi associati alla discendenza caucasica o asiatica. Possono essere inclusi altri biomarcatori e tecnologie, la cui rilevanza scientifica emerge al momento dell'analisi pianificata per le materie incluse nello studio.
    E.3Principal inclusion criteria
    1. Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one but not more than 2 lines of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy;
    2. METex14 skipping alterations, as determined by the central laboratory. Both, archival and
    fresh biopsies are acceptable; In case METex14 skipping alteration has been observed in a subject in a pre-trial setting, it should be ensured that sufficient tissue is available for re-testing before trial entry. Only subjects with METex14 skipping mutation based on trial central testing will be
    enrolled into the trial.
    3. Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure;
    4. Male or female, = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age);
    5. Measurable disease in accordance with RECIST version 1.1;
    6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1."
    7. A female subjects is eligible to participate if she is not pregnant, not
    breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential as defined in Appendix VIII
    OR
    b. A woman of childbearing potential who agrees to use a highly
    effective contraception (i.e., methods with a failure rate of less than 1 %
    per year) as detailed in in Appendix VII of this protocol 2 weeks before
    start of first dose of study treatment, during the treatment period and
    for at least 4 weeks after the last dose of study treatment. Women of
    childbearing potential must have a negative pregnancy test (ß-HCG test
    in serum) prior to enrollment.
    8. A male subject must agree to use and to have their female partners of
    childbearing potential to use a highly effective contraception (i.e.,
    methods with a failure rate of less than 1 % per year) as detailed in
    Appendix VII of this protocol from the first dose of study treatment,
    during the treatment period and for at least 3 months after the last dose
    of study treatment and refrain from donating sperm during this period.
    Male subjects should always use a barrier method such as condom
    concomitantly
    "1. Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one but not more than 2 lines of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy;
    2. METex14 skipping alterations, as determined by the central laboratory. Both, archival and
    fresh biopsies are acceptable; In case METex14 skipping alteration has been observed in a subject in a pre-trial setting, it should be ensured that sufficient tissue is available for re-testing before trial entry. Only subjects with METex14 skipping mutation based on trial central testing will be
    enrolled into the trial.
    3. Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure;
    4. Male or female, = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age);
    5. Measurable disease in accordance with RECIST version 1.1;
    6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1."
    7. A female subjects is eligible to participate if she is not pregnant, not
    breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential as defined in Appendix VIII
    OR
    b. A woman of childbearing potential who agrees to use a highly
    effective contraception (i.e., methods with a failure rate of less than 1 %
    per year) as detailed in in Appendix VII of this protocol 2 weeks before
    start of first dose of study treatment, during the treatment period and
    for at least 4 weeks after the last dose of study treatment. Women of
    childbearing potential must have a negative pregnancy test (ß-HCG test
    in serum) prior to enrollment.
    8. A male subject must agree to use and to have their female partners of
    childbearing potential to use a highly effective contraception (i.e.,
    methods with a failure rate of less than 1 % per year) as detailed in
    Appendix VII of this protocol from the first dose of study treatment,
    during the treatment period and for at least 3 months after the last dose
    of study treatment and refrain from donating sperm during this period.
    Male subjects should always use a barrier method such as condom
    concomitantly
    E.4Principal exclusion criteria
    1. Subjects with characterized EGFR (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations;
    2. Subjects with characterized ALK rearrangements (documented results; local testing acceptable);
    3. Active brain metastases (defined as neurologically stable for < 4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease). Subjects must have completed any prior treatment for brain metastases = 4 weeks prior to start of therapy (= 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids
    are being tapered are eligible. Asymptomatic untreated brain metastases = 1cm are eligible;
    4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy;
    5. Need for transfusion within 14 days prior to the first dose of trial treatment;
    6. Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment;
    7. Inadequate hematological, liver, renal, cardiac function; 8. Prior treatment with other agents targeting the HGF/c-Met pathway; 9. Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years (for a full list of exlustion criteria please see the study protocol).
    1. Subjects with characterized EGFR (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations;
    2. Subjects with characterized ALK rearrangements (documented results; local testing acceptable);
    3. Active brain metastases (defined as neurologically stable for < 4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease). Subjects must have completed any prior treatment for brain metastases = 4 weeks prior to start of therapy (= 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids
    are being tapered are eligible. Asymptomatic untreated brain metastases = 1cm are eligible;
    4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy;
    5. Need for transfusion within 14 days prior to the first dose of trial treatment;
    6. Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment;
    7. Subjects who have brain metastasis as the only measureable lesion;
    8. Inadequate hematological, liver, renal, cardiac function; 9. Prior treatment with other agents targeting the HGF/c-Met pathway; 10. Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years (for a full list of exlustion criteria please see the study protocol).
    E.5 End points
    E.5.1Primary end point(s)
    Objective response rate (confirmed Cr or PR) determinated according to RECIST Version 1.1, based on indipendent review.
    Objective response (confirmed CR or PR) determined according to RECIST Version 1.1, based on independent review.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline up to 20 months
    Baseline up to 20 months
    E.5.2Secondary end point(s)
    1. Objective response rate assessed as per Investigator
    2. Duration of response as assessed by independent review committee
    3. Duration of response as assessed by investigator
    4. Objective disease control Rate as assessed by independent review
    committee
    5. Objective disease control Rate as assessed by investigator
    6. Progression free survival as assessed by independent review
    committee
    7. Progression free survival as assessed by investigator
    8. Overall survival
    9. Number of subjects with TEAEs and deaths
    10. Number of subjects with markedly abnormal vital signs, ECG,
    physical examination and ECOG PS.
    11. Health Related Quality of Life Parameters
    12. Maximum plasma concentration (Cmax) of Drug
    13. Volume of distribution (Vz/F) of drug
    14. Total Clearance (Cl) of drug
    15. Number of subjects with markedly abnormal clinical laboratory tests
    (hematology and coagulation,
    biochemistry and urinalysis).
    1. Objective response rate assessed as per Investigator
    2. Duration of response as assessed by independent review committee
    3. Duration of response as assessed by investigator
    4. Objective disease control Rate as assessed by independent review
    committee
    5. Objective disease control Rate as assessed by investigator
    6. Progression free survival as assessed by independent review
    committee
    7. Progression free survival as assessed by investigator
    8. Overall survival
    9. Number of subjects with TEAEs and deaths
    10. Number of subjects with markedly abnormal vital signs, ECG,
    physical examination and ECOG PS.
    11. Health Related Quality of Life Parameters
    12. Maximum plasma concentration (Cmax) of Drug
    13. Volume of distribution (Vz/F) of drug
    14. Total Clearance (Cl) of drug
    15. Number of subjects with markedly abnormal clinical laboratory tests
    (hematology and coagulation,
    biochemistry and urinalysis).
    E.5.2.1Timepoint(s) of evaluation of this end point
    2, 3, 6, 7: Baseline until PD/ death within 84 days of last tumor
    assessment; assessed up to 20 months
    8: Baseline until death , assessed up to 20 months
    1, 4, 5, 10, 11, 15: Baseline up to 20 months
    9: From the first dose of study drug administration until 33 days after
    the last dose of study drug administration, assessed up to 20 months
    12 to 14: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1
    2, 3, 6, 7: Baseline until PD/ death within 84 days of last tumor
    assessment; assessed up to 20 months
    8: Baseline until death , assessed up to 20 months
    1, 4, 5, 10, 11, 15: Baseline up to 20 months
    9: From the first dose of study drug administration until 33 days after
    the last dose of study drug administration, assessed up to 20 months
    12 to 14: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1
    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 Yes
    E.6.7Pharmacodynamic Yes
    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) 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 No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    NA
    NA
    E.8.2.4Number of treatment arms in the trial1
    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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Belgium
    China
    France
    Germany
    Israel
    Italy
    Japan
    Korea, Democratic People's Republic of
    Korea, Republic of
    Netherlands
    Poland
    Spain
    Switzerland
    Taiwan
    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
    Time point at which all subjects have discontinued trial drug (due to
    either disease progression, undue toxicity or withdrawal, and,
    therefore, are not likely to benefit from tepotinib any longer) and two
    thirds of the subjects have died.
    Time point at which all subjects have discontinued trial drug (due to
    either disease progression, undue toxicity or withdrawal, and,
    therefore, are not likely to benefit from tepotinib any longer) and two
    thirds of the subjects have died.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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: 90
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    the elderly
    anziani
    F.4 Planned number of subjects to be included
    F.4.1In the member state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 80
    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)
    normal treatment
    normale trattamento
    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 Decision2016-05-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-05-18
    P. End of Trial
    P.End of Trial StatusOngoing
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