Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   40165   clinical trials with a EudraCT protocol, of which   6574   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-001845-42
    Sponsor's Protocol Code Number:TAK-788-3001
    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:2021-01-26
    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 number2019-001845-42
    A.3Full title of the trial
    A Randomized Phase 3 Multicenter Open-label Study to Compare the Efficacy of TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR
    Exon 20 Insertion Mutations
    Studio randomizzato di fase 3, multicentrico, in aperto, per confrontare l'efficacia di TAK-788 come trattamento di prima linea rispetto alla chemioterapia a base di platino in pazienti con carcinoma polmonare non a piccole cellule con mutazioni di EGFR da inserzione nell'esone 20
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for NSCLC With EGFR Exon 20 Insertions
    TAK-788 come trattamento di prima linea rispetto alla chemioterapia a base di platino per il NSCLC con inserzioni nell’esone 20 dell’EGFR
    A.3.2Name or abbreviated title of the trial where available
    TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for NSCLC With EGFR Exon 20 Inser
    TAK-788 come trattamento di prima linea rispetto alla chemioterapia a base di platino per il NSCLC c
    A.4.1Sponsor's protocol code numberTAK-788-3001
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN00000000
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00000000
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1232-6059
    A.5.4Other Identifiers
    Name:NANumber:NA
    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 SponsorMILLENNIUM PHARMACEUTICALS, 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 supportTakeda Pharmaceutical Company Limited
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTakeda Pharmaceuticals International, Co
    B.5.2Functional name of contact pointGlobal Medical Information
    B.5.3 Address:
    B.5.3.1Street Address40 Landsowne Street
    B.5.3.2Town/ cityCambridge, MA
    B.5.3.3Post code02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+18446628532
    B.5.5Fax number+18008816092
    B.5.6E-mailGlobalOncologyMedInfo@takeda.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 nameTAK-788
    D.3.2Product code [TAK-788]
    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.3.9.1CAS number 1847461-43-1
    D.3.9.2Current sponsor codeTAK-788
    D.3.9.4EV Substance CodeSUB195427
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 RoleComparator
    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 Alimta
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland B.V
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 namePemetrexed
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPEMETREXED
    D.3.9.1CAS number 137281-23-3
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB09655MIG
    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 RoleComparator
    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 Cisplatin-Losung-Ribosepharm
    D.2.1.1.2Name of the Marketing Authorisation holderHikma Farmacêutica (Portugal), S.A.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCisplatin
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    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 INNCISPLATIN
    D.3.9.1CAS number 15663-27-1
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(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: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Ribocarbo
    D.2.1.1.2Name of the Marketing Authorisation holderHikma Farmacêutica (Portugal), S.A.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCarboplatin
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    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.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number600
    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: 5
    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.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameLoperamide
    D.3.2Product code [NA]
    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.3.9.1CAS number 53179-11-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB02969MIG
    D.3.10 Strength
    D.3.10.1Concentration unit ml millilitre(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    Non-Small Cell Lung Cancer (NSCLC) with EGFR exon 20 insertion mutations
    Carcinoma polmonare non a piccole cellule (Non-Small Cell Lung Cancer, [NSCLC]) con mutazioni dell’esone 20 dell’EGFR
    E.1.1.1Medical condition in easily understood language
    Non-Small Cell Lung Cancer (NSCLC)
    Carcinoma polmonare non a piccole cellule (NSCLC)
    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 LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    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
    To compare the efficacy of TAK-788 as first-line treatment with that of platinum-based chemotherapy in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations, as evidenced by progression-free survival (PFS) as assessed by blinded independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    Confrontare l’efficacia di TAK-788 come trattamento di prima linea rispetto all’efficacia della chemioterapia a base di platino in pazienti affetti da NSCLC localmente avanzato o metastatico i cui tumori ospitano mutazioni di inserzione dell’esone 20 dell’EGFR, come evidenziato dalla sopravvivenza libera da progressione (Progression-Free Survival, [PFS]) in base alla valutazione in cieco da parte di un comitato di revisione indipendente (Independent Review Committee, [IRC]), secondo i criteri di valutazione della risposta nei tumori solidi (Response Evaluation Criteria In Solid Tumors, [RECIST]) versione 1.1.
    E.2.2Secondary objectives of the trial
    -To compare secondary measures of clinical efficacy of TAK-788 to that of platinum-based chemotherapy, as evidenced by confirmed objective response rate (ORR), time to response, duration of response, disease control rate (DCR), and overall survival (OS).
    -To compare patient-reported symptoms (particular core symptoms of lung cancer), functioning, and health-related quality of life (HRQoL) with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the EORTC lung cancer module, QLQ-LC13, in patients treated with TAK-788 compared with those treated with platinum-based chemotherapy.
    -To collect pharmacokinetics (PK) of TAK-788 and its active metabolites, AP32960 and AP32914, to contribute to population PK and exposure response analyses (TAK-788 group only).
    Confrontare misure secondarie di efficacia clinica di TAK-788 con quelle della chemioterapia a base di platino,come evidenziato dal tasso di risposta obiettiva confermato,dal tempo alla risposta,dalla durata della risposta,dal tasso di controllo della malattia e sopravvivenza complessiva/Confrontare sintomi riferiti dal paziente(in particolare sintomi chiave del carcinoma polmonare),funzionalità e qualità della vita correlata alla salute,usando Questionario per misurare la qualità della vita-Modulo principale a 30 voci dell’Organizzazione europea per la ricerca e il trattamento dei tumori e Questionario per misurare la qualità della vita-Modulo sul carcinoma polmonare a 13 voci dell’EORTC,in pazienti trattati con TAK-788 rispetto a quelli trattati con chemioterapia a base di platino/Raccogliere dati sulla farmacocinetica di TAK-788 e suoi metaboliti attivi,AP32960 e AP32914,per contribuire alle analisi PK di popolazione e analisi rapporto risposta/esposizione(solo braccio con TAK-788)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each patient must meet all the following inclusion criteria to be randomized to treatment:
    1. Male or female adult patients (aged 18 years or older, or as defined per local regulations).
    2. Histologically or cytologically confirmed locally adfor definitive therapy, recurrent, or metastatic (Stage IV) NSCLC.
    3. A documented EGFR in-frame exon 20 insertion mutation (including A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, or any other in-frame exon 20 insertion mutation) assessed by a Clinical Laboratory Improvements
    Amendment (CLIA)-certified (United States [US] sites) or an accredited (outside of the US) local laboratory. The local molecular testing reports may be required by the sponsor to confirm the exon 20 insertion mutation status. The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR mutations for which there are approved EGFR TKIs (ie, exon 19 del,L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid).
    4. Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR in-frame exon 20 insertion mutation (see laboratory manual). Note: confirmation of central test positivity is not required before randomization.
    5. At least 1 measurable lesion per RECIST version 1.1 (Appendix D). Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy.
    6. Life expectancy =3 months.vanced not suitable
    7. Eastern Cooperative Oncology Group (ECOG) performance status of 0
    to 1 (Appendix E).
    8. Adequate organ and hematologic function, as determined by the
    following:
    a) Alanine aminotransferase/aspartate aminotransferase =2.5 times the
    upper limit of the normal range (ULN; =5 times the ULN is acceptable if
    liver metastases are present).
    b) Total serum bilirubin =1.5 times the ULN (=3.0 times the ULN for
    patients with Gilbert syndrome or if liver metastases are present).
    c) Estimated creatinine clearance =45 mL/min (calculated by using the
    Cockcroft-Gault equation) [35].
    d) Serum albumin =2 g/dL.
    e) Serum lipase =1.5 times the ULN.
    f) Serum amylase =1.5 times the ULN unless the increased serum
    amylase is due to salivary isoenzymes.
    g) Absolute neutrophil count =1500/µL.
    h) Platelets =100,000/µL.
    i) Hemoglobin =9 g/dL.
    9. Normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of =450 milliseconds in males or = 470 milliseconds in females.
    Ciascun paziente deve soddisfare tutti i seguenti criteri di inclusione per essere randomizzato al trattamento:
    1. Pazienti ambosesso adulti (di età pari o superiore a 18 anni, o come definito in base alle normative locali).
    2. NSCLC (stadio IV) ricorrente o metastatico, non idoneo per la terapia definitiva, localmente avanzato, confermato istologicamente o citologicamente.
    3. Una mutazione in-frame da inserzione nell’esone 20 dell’EGFR documentata (comprese A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, o qualsiasi altra mutazione in-frame di inserzione nell’esone 20), valutata da un laboratorio locale con certificazione conforme agli Emendamenti per il miglioramento dei laboratori clinici (Clinical Laboratory Improvements Amendment, [CLIA]) (per i centri statunitensi) o accreditato (al di fuori degli Stati Uniti). Lo sponsor potrebbe richiedere le relazioni relative all’analisi molecolare locale per confermare lo stato della mutazione da inserzione nell’esone 20. La mutazione da inserzione nell’esone 20 dell’EGFR può essere unica o in combinazione con altre mutazioni dell’EGFR o del recettore del fattore di crescita epidermico umano 2 (Human Epidermal Growth Factor Receptor 2, [HER2]), escluse le mutazioni dell’EGFR per le quali non esistono TKI dell’EGFR approvati (ossia, delezione dell’esone 19, L858R, T790M, L861Q, G719X o S768I, dove X è un qualsiasi altro aminoacido).
    4. Adeguato tessuto tumorale disponibile da siti primati o metastatici, per la conferma da parte del laboratorio centrale della mutazione in-frame da inserzione dell’esone 20 dell’EGFR (vedere il Manuale di laboratorio). Nota: la conferma di positività dell’analisi centrale non è necessaria prima della randomizzazione.
    5. Almeno 1 lesione misurabile secondo i criteri RECIST versione 1.1 (Appendice D). Le lesioni irradiate in precedenza non possono essere utilizzate come lesioni target, a meno che non vi sia un’inequivocabile progressione radiologica dopo la radioterapia.
    6. Aspettativa di vita = 3 mesi.
    7. Valutazione della prestazione da 0 a 1 nella scala dell’Eastern Cooperative Oncology Group (ECOG) (Appendice E).
    8. Adeguata funzione ematologica e d’organo, come determinato dai seguenti parametri:
    a) Alanina aminotransferasi/Aspartato aminotransferasi = 2,5 volte il limite superiore alla norma (Upper Limit of Normal, [ULN]; in presenza di metastasi epatiche sono accettabili valori = 5 volte l’ULN).
    b) Bilirubina sierica totale = 1,5 volte l’ULN (= 3 volte l’ULN per pazienti con sindrome di Gilbert o in presenza di metastasi epatiche).
    c) Clearance della creatinina = 45 ml/min (calcolata mediante l’equazione di Cockcroft-Gault) [35].
    d) Albumina sierica = 2 g/dl.
    e) Lipasi sierica = 1,5 volte l’ULN.
    f) Amilasi sierica = 1,5 volte l’ULN a meno che l’aumento di amilasi sierica sia dovuto a isoenzimi salivari.
    g) Conta assoluta dei neutrofili = 1.500/µl.
    h) Piastrine = 100.000/µl.
    i) Emoglobina = 9 g/dl.
    9. Intervallo QT normale alla valutazione dell’elettrocardiogramma (ECG) di screening, definito come intervallo QT corretto (con la formula di Fridericia) (QTcF) = 450 millisecondi nei soggetti di sesso maschile o = 470 millisecondi nei soggetti di sesso femminile.
    E.4Principal exclusion criteria
    Patients meeting any of the following exclusion criteria are not to be
    randomized to treatment.
    1. Female patients who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period.
    Note: Female patients who are lactating will be eligible if they discontinue breastfeeding.
    2. Current treatment in another therapeutic clinical study.
    3. Received prior systemic treatment for locally advanced or metastatic disease (with the exception below): Neoadjuvant or adjuvant chemotherapy/immune therapy for Stage I to III or combined modality chemotherapy/radiation for locally advanced disease is allowed if completed >6 months before the development of metastatic disease.
    4. Received radiotherapy =14 days before randomization or has not recovered from radiotherapy-related toxicities. Palliative radiation administered outside the chest and brain, stereotactic radiosurgery, and stereotactic body radiotherapy are allowed up to 7 days before randomization.
    5. Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer (Appendix F) within 10 days before randomization.
    6. Had major surgery within 28 days before randomization. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
    7. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
    8. Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions). Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring
    corticosteroids to control symptoms within 7 days before randomization and have no evidence of new or enlarging brain metastases
    9. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
    I pazienti che soddisfano uno qualsiasi dei seguenti criteri di esclusione non saranno randomizzati al trattamento.
    1. Pazienti di sesso femminile che allattano al seno o presentano un risultato positivo al test di gravidanza sul siero o sulle urine durante il periodo di screening. Nota: le pazienti che allattano saranno idonee se interrompono l’allattamento al seno.
    2. Trattamento attuale in un altro studio clinico terapeutico.
    3. Precedente assunzione di trattamento sistemico per la malattia localmente avanzata o metastatica (eccetto quanto segue):
    È consentita la chemioterapia neoadiuvante o adiuvante/immunoterapia per lo stadio da I a III oppure la combinazione di chemioterapia/radioterapia per la malattia localmente avanzata se completata > 6 mesi prima dello sviluppo della malattia metastatica.
    4. Pazienti che hanno ricevuto radioterapia = 14 giorni prima della randomizzazione o che presentano una ripresa non completa da tossicità correlate alla radioterapia. Sono consentite la radioterapia palliativa somministrata al di fuori del torace e del cervello, la radiochirurgia stereotassica e la radioterapia stereotassica corporea fino a 7 giorni prima della randomizzazione.
    5. Assunzione di un inibitore moderato o forte del citocromo P-450 (CYP)3A o un induttore moderato o forte del CYP3A (Appendice F) entro 10 giorni prima della randomizzazione.
    6. Intervento di chirurgia maggiore nei 28 giorni precedenti la randomizzazione. Sono consentite procedure chirurgiche minori come il posizionamento di un catetere o biopsie minimamente invasive.
    7. Pazienti cui sia stato diagnosticato un altro tumore maligno primario diverso da NSCLC, ad eccezione del tumore cutaneo diverso dal melanoma adeguatamente trattato o del tumore della cervice in situ; carcinoma prostatico non metastatico trattato in modo definitivo; o pazienti con un altro tumore maligno primario che sono liberi da recidiva e con almeno 3 anni trascorsi dalla diagnosi dell’altro tumore maligno primario.
    8. Presenza di metastasi cerebrali attive note (presenza di metastasi intracraniche nel sistema nervoso centrale [SNC] precedentemente non trattate o metastasi intracraniche nel SNC precedentemente trattate con lesioni del SNC di nuova insorgenza o in fase di progressione documentate mediante esame radiologico). È consentita la presenza di metastasi cerebrali qualora trattate con chirurgia e/o radiazione e se sono rimaste stabili senza bisogno di corticosteroidi per controllare i sintomi nei 7 giorni precedenti la randomizzazione, e se non vi sono evidenze di metastasi cerebrali nuove o in accrescimento.
    9. Compressione del midollo spinale in corso (sintomatica o asintomatica e rilevata mediante esame radiografico di diagnostica per immagino) o malattia leptomeningea (sintomatica o asintomatica).
    E.5 End points
    E.5.1Primary end point(s)
    PFS, as assessed by the IRC, per RECIST version 1.1.
    PFS, come valutata dall’IRC, in base ai criteri RECIST versione 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The final analyses for the primary endpoint will be conducted after approximately 227 to 270 IRC-assessed PFS events (PD or death) have occurred. The number of events required will be determined according to a prespecified event size adaptation rule (see Section 13.2). The estimated time frame for primary completion is 32 to 40 months after
    the first patient is randomized. The final analysis (FA) for the primary endpoint could occur earlier if the interim analysis (IA) results are statistically significant
    Le analisi finali per l’endpoint primario saranno condotte dopo che si saranno verificati all’incirca 227-270 eventi di PFS valutata dall’IRC (progressione della malattia [Progressive Disease, (PD)] o decesso). Il numero di eventi richiesto sarà determinato in base a una regola di adeguamento delle dimensioni dell’evento prespecificata (vedere Sezione 13.2). L’intervallo di tempo stimato per il completamento primario è di 32-40 mesi dopo la randomizzazione del primo paziente. L’analisi finale (AF) per l’endpoint primario potrebbe avvenire prima se l’analisi ad interim (AI) dà risultati statisticamente significativi
    E.5.2Secondary end point(s)
    The key secondary endpoints are:
    • Confirmed ORR, as assessed by the IRC, per RECIST version 1.1.
    • OS.
    The other secondary endpoints are:
    • PFS, as assessed by the investigator.
    • Confirmed ORR, as assessed by the investigator.
    • Duration of response, as assessed by the IRC and the investigator.
    • Time to response, as assessed by the IRC and the investigator.
    • DCR, as assessed by the IRC and the investigator.
    • Patient-reported symptoms (particular core symptoms of lung cancer),
    functioning, and HRQoL with the EORTC QLQ-C30 and QLQ-LC13.
    Gli endpoint secondari fondamentali sono:
    • ORR confermato, come valutato dall’IRC, in base ai criteri RECIST versione 1.1.
    • OS.
    Gli altri endpoint secondari sono:
    • PFS, come valutata dallo sperimentatore.
    • ORR confermato, come valutato dallo sperimentatore.
    • Durata della risposta, come valutata dall’IRC e dallo sperimentatore.
    • Tempo alla risposta, come valutato dall’IRC e dallo sperimentatore.
    • DCR, come valutato dall’IRC e dallo sperimentatore.
    • Sintomi riferiti dal paziente (sintomi principali specifici di carcinoma polmonare), funzionalità e HRQoL valutata mediante i questionari EORTC QLQ-C30 e QLQLC13.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the time of the primary endpoint analysis
    Al momento dell’analisi dell’endpoint primario
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA75
    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
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Canada
    China
    Denmark
    France
    Germany
    Greece
    Hong Kong
    Israel
    Italy
    Japan
    Korea, Democratic People's Republic of
    Korea, Republic of
    Portugal
    Russian Federation
    Singapore
    Spain
    Sweden
    Switzerland
    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
    LPLV
    LPLV
    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: 218
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-01-26. Yes
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 318
    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)
    Terminated for those who no longer benefit from TAK-788, the benefitrisk no longer favors the individual, if TAK-788 becomes available either commercially or via another access mechanism, or when an
    alternative appropriate therapy becomes available. Posttrial access may be terminated in a country or geographical region where marketing authorization has been rejected, the development of TAK788 has been suspended or stopped by the sponsor, or TAK-788 can no longer be supplied
    Terminato per coloro che non traggono più beneficio, se rapporto rischi/benefici non è più a favore del soggetto,seTAK-788 diventa disponibile a livello commerciale o per altro meccanismo di accesso,o se si rende disponibile una terapia alternativa appropriata.L’accesso post-sperimentazione potrà essere interrotto in Paese o regione in cui l’autorizzazione all’immissione in commercio è stata rifiutata, lo sviluppo di TAK 788 sospeso o interrotto dallo sponsor,o TAK-788 non può più essere fornito
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-04-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-11
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA