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    Summary
    EudraCT Number:2020-005048-46
    Sponsor's Protocol Code Number:D9673C00007
    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:2021-06-08
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-005048-46
    A.3Full title of the trial
    An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously-Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12)
    Studio di fase 3b/4, in aperto, internazionale, multicentrico, di trastuzumab deruxtecan in pazienti con o senza metastasi cerebrali al basale affetti da carcinoma mammario HER2-positivo avanzato/metastatico precedentemente trattato (DESTINY-Breast12)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to investigate the efficacy and safety of trastuzumab deruxtecan in patients With or Without Brain Metastasis Who Have Previously-Treated Advanced or Metastatic HER2 Positive Breast Cancer
    Studio per valutare l'efficacia e la sicurezza di trastuzumab durextecan in pazienti con o senza metastasi cerebrali al basale affette da carcinoma mammario HER2-positivo avanzato o metastatico precedentemente trattato
    A.3.2Name or abbreviated title of the trial where available
    DESTINY-Breast12
    DESTINY-Breast12
    A.4.1Sponsor's protocol code numberD9673C00007
    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 SponsorASTRAZENECA AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation Center
    B.5.3 Address:
    B.5.3.1Street AddressNA
    B.5.3.2Town/ cityNA
    B.5.3.3Post codeNA
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@astrazeneca.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 nameTrastuzumab Deruxtecan
    D.3.2Product code [DS-8201a]
    D.3.4Pharmaceutical form Powder for 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 INNTrastuzumab Deruxtecan
    D.3.9.1CAS number 1599440-13-7
    D.3.9.2Current sponsor codeDS-8201a
    D.3.9.3Other descriptive nameT-DXd
    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) Yes
    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 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 Yes
    D.3.11.13.1Other medicinal product typeFarmaco anticorpo coniugato
    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
    Treatment of patients with HER2-positive breast cancer with or without brain metastasis
    Trattamento di pazienti affetti da carcinoma mammario HER2-positivo con o senza metastasi cerebrali
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic HER2-positive breast cancer
    Carcinoma mammario HER2-positivo avanzato o metastatico
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10065430
    E.1.2Term HER2 positive breast 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
    To describe the overall treatment effect of T-DXd in HER2+ MBC patients with or without baseline brain metastasis
    Descrivere l’effetto complessivo del trattamento con T-DXd in pazienti affetti da MBC HER2+ con o senza metastasi cerebrali al basale
    E.2.2Secondary objectives of the trial
    1. To describe the treatment effect on the development and progression of brain metastasis in patients with or without baseline brain metastasis using additional efficacy measurements
    2. To describe efficacy in patients with stable or untreated brain metastasis
    3. To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC patients with or without baseline brain metastasis
    4. To describe the safety profile of T-DXd
    1. Descrivere l’effetto del trattamento sullo sviluppo e sulla progressione di metastasi cerebrali in pazienti con o senza metastasi cerebrali al basale usando ulteriori misurazioni dell’efficacia
    2. Descrivere l’efficacia in pazienti con metastasi cerebrali stabili o non trattate
    3. Descrivere l’effetto di T-DXd sui sintomi, sulle condizioni e sulla HRQoL in pazienti affetti da MBC HER2+ con o senza metastasi cerebrali al basale
    4. Descrivere il profilo di sicurezza di T-DXd
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Key inclusion Criteria:
    1. Pathologically documented breast cancer that:
    (a) Is unresectable/advanced or metastatic, and
    (b) Has confirmed HER2+ expression
    2. Participant must have either:
    (a) No evidence of BM, or
    (b) Untreated BM not needing immediate local therapy, or
    - For participants with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the study physician is required prior to enrollment, or
    (c) Previously treated stable or progressing BM
    - Previously treated BM with local therapy may either be radiographically stable for >= 4 weeks since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
    - Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study who also have other sites of disease assessable by RECIST 1.1
    3. Participants with brain metastases must be neurologically stable and:
    (a) Be receiving the equivalent of dexamethasone <= 2 mg/day
    (b) If receiving an anticonvulsant regimen, the regimen must have been stable for >= 14 days
    (c) Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
    4. Radiologic or objective evidence of disease progression on trastuzumab, pertuzumab, or T-DM1 (<= 2 lines/regimens of therapy in the metastatic setting)
    1. Carcinoma mammario patologicamente documentato che:
    (a) Non è resecabile/avanzato o metastatico, e
    (b) Ha confermato l’espressione HER2+
    2. Il partecipante deve avere:
    (a) Nessuna evidenza di BM, o
    (b) BM non trattato che non necessita di terapia locale immediata, o
    - Per i partecipanti con lesioni dell’SNC non trattate > 2,0 cm durante lo screening della risonanza magnetica cerebrale con contrasto, è richiesta la discussione e l’approvazione del medico dello studio prima dell’arruolamento, o
    (c) BM stabile o in progressione precedentemente trattato
    - BM precedentemente trattato con terapia locale può essere radiograficamente stabile per >= 4 settimane dal trattamento o può essere progredito dalla precedente terapia locale nell’SNC, a condizione che non vi siano indicazioni cliniche per un immediato trattamento con terapia locale
    - Pazienti trattati con terapia locale nell’SNC per lesioni di nuova identificazione riscontrati durante la risonanza magnetica cerebrale con contrasto eseguita durante lo screening di questo studio che hanno anche altre mattie valutabili da RECIST 1.1
    3. I partecipanti con metastasi cerebrali devono essere neurologicamente stabili e:
    (a) Ricevere l’equivalente di desametasone <= 2 mg/giorno
    (b) Se si riceve un regime anticonvulsivante, il regime deve essere rimasto stabile per >= 14 giorni
    (c) Devono essere disponibili le pertinenti registrazioni di qualsiasi trattamento dell’SNC per consentire la classificazione delle lesioni target e non-target
    4. Evidenza radiologica o oggettiva di progressione della malattia su trastuzumab, pertuzuma o T-DM1 (<= 2 linee/regime di terapia in ambito metastatico)
    E.4Principal exclusion criteria
    1. Known or suspected LMD
    2. Prior exposure to tucatinib treatment
    3. Based on screening brain MRI, participants must not have any of the following:
    (a) Any untreated brain lesions > 2.0 cm in size
    (b) Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent).
    (c) Any brain lesion thought to require immediate local therapy,
    (d) Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy
    4. Has spinal cord compression
    1. LMD noto o sospetto
    2. Precedente esposizione al tattamento con tucatinib
    3. Sulla base dello screening MRI cerebrale, i partecipanti non devono avere nessuno dei seguenti:
    (a) Qualsiasi lesione cerebrale non trattata di dimensioni > 2,0 cm
    (b) Uso continuo di corticosteroidi sistemici per il controllo dei sintomi delle metastasi cerebrali a una dose giornaliera totale > 2 mg di desametasone (o equivalente)
    (c) Qualsiasi lesione cerebrale che si ritiene richieda una terapia locale immediata
    (d) Ha crisi epilettiche parziali generalizzate o complesse scarsamente controllate (> 1/settimana) o manifesta progressione neurologica a causa delle metastasi cerebrali nonostante la terapia diretta all’SNC
    4. Ha la compressione del midollo spinale
    E.5 End points
    E.5.1Primary end point(s)
    Participants without BM at baseline (Cohort 1):
    - ORR by RECIST 1.1
    Participants with BM at baseline (Cohort 2):
    - PFS by RECIST 1.1
    Partecipanti senza BM al basale (Coorte 1):
    - ORR secondo RECIST 1.1
    Partecipanti con BM al basale (Coorte 2):
    - PFS secondo RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assessed until progression or death
    Valutato fino a progressione o morte
    E.5.2Secondary end point(s)
    1. Participants in both cohorts:
    - OS
    - DoR
    - Time to progression
    - DoT on subsequent lines of therapy
    - PFS2
    Participants without BM at baseline (Cohort 1):
    - Incidence of new symptomatic CNS metastasis during treatment
    In patients who develop isolated CNS progression, receive local therapy, and continue on protocol therapy:
    - Time to next progression (CNS or extracranial) or death
    - Site (CNS vs extracranial vs both) of next progression
    2. Participants with BM at baseline (Cohort 2):
    - ORR by RECIST 1.1
    - CNS PFS (time to CNS progression or death)
    - Time to new CNS lesions
    - ORR in brain by RECIST 1.1 as determined by ICR
    - DoR in brain
    3. Changes in symptoms, functioning, and HRQoL as measured by
    - All patients: EORTC QLQ-C30, NANO scale, Cognitive Tests
    - BM patients: MDASI brain tumor-specific items
    - ILD/pneumonitis patients: SGRQ-I
    4. - Rate of treatment-related AEs by CTCAE
    - Rate of investigator-assessed ILD/pneumonitis
    - Rate of AEs among patients with baseline BM who are treated with concurrent high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent)
    5. Presence of ADAs for T-DXd
    1. Partecipanti in entrambe le coorti:
    - OS
    - DoR
    - Tempo alla progressione
    - DoT in successive linee di terapia
    - PFS2
    Partecipanti senza BM al basale (Coorte 1):
    - Incidenza di nuove metastasi sintomatiche nell’SNC durante il trattamento
    Nei pazienti che sviluppano progressione isolata nell’SNC, sono sottoposti a terapia locale e proseguono la terapia prevista dal protocollo:
    - Tempo alla progressione successiva (SNC o extracranica) o decesso
    - Sito (SNC rispetto a extracranico rispetto a entrambi) della progressione successiva
    2. Partecipanti con BM al basale (Coorte 2):
    - ORR secondo RECIST 1.1
    - PFS dell’SNC (tempo alla progressione dell’SNC o decesso)
    - Tempo a nuove lesioni nell’SNC
    - ORR nell’encefalo secondo quanto determinato da ICR mediante RECIST 1.1
    - DoR nell’encefalo
    3. Variazioni dei sintomi, delle condizioni e della HRQoL, misurate mediante
    - Tutti i pazienti: QLQ a 30 voci di EORTC, scala NANO. Test cognitivi
    - Pazienti con BM: Voci specifiche del tumore cerebrale in MDASI
    - Pazienti con ILD/polmonite: SGRQ-I
    4. - Tasso di EA correlati al trattamento mediante CTCAE
    - Tasso di ILD/polmonite valutato dallo sperimentatore
    - Tasso di EA tra pazienti con BM al basale trattati con steroidi concomitanti ad alto dosaggio (dose giornaliera totale di desametasone o equivalente > 2 mg)
    5. Presenza di ADA anti-T-DXd
    E.5.2.1Timepoint(s) of evaluation of this end point
    The timepoints for key secondary endpoints are: please see section secondary endpoints for corresponding timepoints below
    - assessed until progression or death
    - AEs and SAEs throughout the treatment period and including the safety follow-up (40+ up to 7 days after discontinuation of all study interventions)
    Il tempo per gli obiettivi secondari chiave sono: vedere la sezione degli endpoint secondari per il tempo corrispondente qui di seguito:
    - valutato fino a progressione o morte
    - AE e SAE durante il periodo di trattamento e incluso il follow-up di sicurezza (da 40+ fino a 7 giorni dopo l’interruzione di tutti gli interventi dello studio)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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) Yes
    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 Yes
    E.8.1.7.1Other trial design description
    2 Coorti
    2 cohorts
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA52
    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
    Australia
    Canada
    Japan
    Russian Federation
    United States
    Belgium
    Denmark
    Finland
    Germany
    Ireland
    Italy
    Netherlands
    Norway
    Poland
    Portugal
    Spain
    Sweden
    Switzerland
    United Kingdom
    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
    Completing the last expected visit/contact of the last patient undergoing the study.
    He/she has completed all phases of the study as per SoAs (including follow-up for OS).
    Completamento dell’ultima visita /contatto previsto dall’ultimo paziente dello studio.
    Lui/lei ha completato tutte le fasi dello studio come da programma delle attività (SoA) (incluso il follow-up per OS).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days22
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days25
    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: 400
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state64
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 333
    F.4.2.2In the whole clinical trial 500
    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)
    After final DCO for this study, AZ will continue to supply T-DXd to participants who received T-DXd until meeting any discontinuation criteria as defined in Protocol. Where possible, if commercial T-DXd is available in local market then this route should be used. In the event that a roll-over or safety extension study is available at time of final DCO and DB closure, participants currently receiving T-DXd treatment may be transitioned to such a study and would be asked to sign a new ICF.
    Dopo il DCO finale dello studio, AZ continuerà a fornire T-DXd ai partecipanti che hanno ricevuto T-DXd, fino al raggiungimento di qualsiasi criterio di interruzione come definito dal protocollo. Laddove possibile, se T-DXd sarà disponibile in commercio sul mercato locale, verrà utilizzato questo approccio. Nel caso sia disponibile uno studio di roll-over o di estensione della sicurezza al momento del DCO finale e della chiusura del DB, i partecipanti che attualmente ricevuto il 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 Decision2021-05-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-02-24
    P. End of Trial
    P.End of Trial StatusOngoing
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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