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    Summary
    EudraCT Number:2019-004833-18
    Sponsor's Protocol Code Number:MS200647_0020
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-07-14
    Trial results View 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 number2019-004833-18
    A.3Full title of the trial
    A Phase II, Multicenter, Open Label Study of Bintrafusp alfa (M7824) Monotherapy in Participants with HMGA2-expressing Triple Negative Breast Cancer
    Studio di fase II, multicentrico, in aperto volto a valutare bintrafusp alfa (M7824) in monoterapia in partecipanti con carcinoma mammario triplo negativo esprimente il gruppo ad alta mobilità AT-gancio 2 (HMGA2
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Bintrafusp alfa in HMGA2-expressing Triple Negative Breast Cancer
    Bintrafusp alfa nel carcinoma mammario triplo negativo esprimente HMGA2
    A.4.1Sponsor's protocol code numberMS200647_0020
    A.5.4Other Identifiers
    Name:IND numberNumber:146863
    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 Healthcare 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 Healthcare KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Healthcare KGaA
    B.5.2Functional name of contact pointCommunication Center Merck KGaA
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Strasse 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.3.4CountryGermany
    B.5.4Telephone number+49 6151 72 5200
    B.5.5Fax number+49 6151 72 2000
    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 namebintrafusp alfa
    D.3.2Product code M7824
    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 INNbintrafusp alfa
    D.3.9.2Current sponsor codeM7824
    D.3.9.3Other descriptive nameMSB0011359C
    D.3.9.4EV Substance CodeSUB179957
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) 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 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
    Triple Negative Breast Cancer
    carcinoma mammario triplo negativo
    E.1.1.1Medical condition in easily understood language
    Triple Negative Breast Cancer
    carcinoma mammario triplo negativo
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10075566
    E.1.2Term Triple negative 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 evaluate clinical efficacy of bintrafusp alfa in participants with TNBC with high HMGA2 expression, based on ORR
    Valutare l’efficacia clinica di bintrafusp alfa, in partecipanti affetti da TNBC con espressione elevata di HMGA2, in base all’ORR
    E.2.2Secondary objectives of the trial
    To evaluate clinical efficacy of bintrafusp alfa based on DOR
    To evaluate clinical efficacy of bintrafusp alfa based on DRR
    To evaluate clinical efficacy based on PFS
    To evaluate ORR, DOR, DRR, and PFS by Investigator read
    To evaluate clinical efficacy based on OS
    To evaluate clinical safety of bintrafusp alfa
    To characterize the PK profile of bintrafusp alfa
    To characterize the immunogenicity of bintrafusp alfa
    Valutare l’efficacia clinica di bintrafusp alfa in base alla DOR
    Valutare l’efficacia clinica di bintrafusp alfa in base al DRR
    Valutare l’efficacia clinica in base alla PFS
    Valutare ORR, DOR, DRR e PFS mediante lettura da parte dello sperimentatore
    Valutare l’efficacia clinica in base alla OS
    Valutare la sicurezza clinica di bintrafusp alfa
    Caratterizzare il profilo farmacocinetico (PK) di bintrafusp alfa
    Caratterizzare l’immunogenicità di bintrafusp alfa
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Study participants are ≥ 18 years of age at the time of signing the informed consent.
    2. Study participants have histologically or cytologically confirmed TNBC.
    • Absence of HER2, estrogen receptor, and progesterone receptor expression must be documented (criteria for defining TNBC are outlined in the protocol).
    • Participants must have received at least one line of systemic therapy for metastatic disease and have progressed on the line of therapy immediately prior to study entry. There is no limit to the number of prior therapies.
    • Participants may prescreen for HMGA2 expression while on preceding treatment, however screening should only occur if in the opinion of the Investigator, the participant would likely be eligible for study within 6 months.
    3. Participants must have measurable disease.
    4. Availability of either archival tumor tissue or fresh core or excisional biopsy of a tumor lesion (primary or metastatic, excluding bone biopsies) is mandatory to determine HMGA2 expression level prior to enrollment.
    5. HMGA2 high tumor expression is required and will be determined by a central lab.
    6. Participants who have Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.
    7. Participants have a life expectancy ≥ 12 weeks as judged by the Investigator at study start.
    8. Participants have adequate hematological, hepatic and renal and coagulation function as defined in the protocol.
    9. Participants with known HIV infections are in general eligible if the criteria as defined in the protocol are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019).
    10. Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections are in general eligible if the criteria as defined in the protocol are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019).

    Other protocol defined inclusion criteria could apply.
    1. I partecipanti allo studio hanno un’età =18 anni al momento della firma del consenso
    informato.
    2. I partecipanti allo studio presentano TNBC confermato istologicamente o
    citologicamente.
    • Deve essere documentata l’assenza dell’espressione di HER2, del recettore
    estrogenico e del recettore del progesterone (i criteri per definire il TNBC sono
    indicati nel protocollo).
    • I partecipanti devono aver ricevuto almeno una linea di terapia sistemica per malattia
    metastatica e aver mostrato progressione durante tale linea di terapia
    immediatamente
    prima dell’ingresso nello studio. Non vi è alcun limite al numero di terapie precedenti.
    • I partecipanti possono essersi sottoposti al pre-screening dell’espressione di HMGA2
    durante il precedente trattamento; tuttavia, lo screening deve avvenire solo se, a
    giudizio dello sperimentatore, il partecipante risulterebbe probabilmente idoneo allo
    studio entro 6 mesi.
    3. I partecipanti devono presentare malattia misurabile.
    4. È obbligatoria la disponibilità di tessuto tumorale d’archivio o di un’agobiopsia o
    biopsia escissionale fresca di una lesione tumorale (primaria o metastatica, escluse
    le biopsie ossee) per determinare il livello di espressione di HMGA2 prima
    dell’arruolamento.
    5. È richiesta un’elevata espressione tumorale di HMGA2, che sarà determinata da un
    laboratorio centrale.
    6. Partecipanti che presentano uno stato prestazionale (PS) di 0 o 1 secondo l’Eastern
    Cooperative Oncology Group (ECOG).
    7. All’inizio dello studio, i partecipanti presentano un’aspettativa di vita =12
    settimane a giudizio dello sperimentatore.
    8. I partecipanti presentano un’adeguata funzionalità ematologica, epatica, renale e
    coagulativa, secondo quanto definito nel protocollo.
    9. I partecipanti con infezioni note da HIV sono in generale idonei purché risultino
    soddisfatti i criteri specificati nel protocollo (Linee guida dell’FDA sull’idoneità
    alle sperimentazioni cliniche sui tumori, marzo 2019).
    10. I partecipanti con infezioni da virus dell’epatite B (HBV) e/o epatite C (HCV) sono
    in generale idonei purché risultino soddisfatti i criteri specificati nel protocollo
    (Linee guida dell’FDA sull’idoneità alle sperimentazioni cliniche sui tumori, marzo
    2019).
    Possono essere applicati altri criteri di inclusione definiti dal protocollo
    E.4Principal exclusion criteria
    1. Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study intervention.
    2. Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids
    3. Participants must not have received prior cancer treatment with any other immunotherapy or checkpoint inhibitors, or any other immune-modulating monoclonal antibody.
    4. Participants that received any organ transplantation, including stem-cell transplantation, but with the exception of transplants that do not require immunosuppression.
    5. Participants with significant acute or chronic infections.
    6. Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
    7. Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia.

    Other protocol defined exclusion criteria could apply.
    1. Sono esclusi i partecipanti con metastasi attive del sistema nervoso centrale (SNC)
    che provocano sintomi clinici o metastasi che richiedono l’intervento terapeutico. I
    partecipanti con anamnesi di metastasi del SNC trattate (con intervento chirurgico o
    radioterapia) non sono idonei, a meno che non si siano completamente ristabiliti dal
    trattamento, non abbiano dimostrato progressione per almeno 4 settimane e non
    stiano assumendo steroidi da almeno 7 giorni prima dell’inizio dell’intervento in s
    studio.
    2. Partecipanti con malattia polmonare interstiziale o precedente anamnesi di polmonite
    che abbia richiesto l’uso di steroidi per via orale o endovenosa (EV)
    3. I partecipanti non devono aver ricevuto un precedente trattamento antitumorale con
    qualsiasi altra immunoterapia o inibitori del checkpoint, o qualsiasi altro anticorpo
    monoclonale immunomodulante.
    4. Partecipanti che hanno ricevuto un trapianto d’organo, incluso il trapianto di
    cellule staminali, ma esclusi i trapianti che non richiedono immunosoppressione.
    5. Partecipanti con infezioni acute o croniche significative.
    6. Partecipanti con malattia autoimmune in fase attiva che potrebbe peggiorare durante
    il trattamento con un agente immunostimolante.
    7. Partecipanti con malattie cardiovascolari/cerebrovascolari clinicamente significative,
    tra cui: incidente cerebrovascolare/ictus, infarto del miocardio, angina
    instabile, scompenso cardiaco congestizio o aritmia cardiaca seria.
    Possono essere applicati altri criteri di esclusione definiti dal protocollo
    E.5 End points
    E.5.1Primary end point(s)
    Confirmed objective response according to RECIST 1.1 assessed by an IRC
    Risposta obiettiva confermata, valutata da un IRC secondo i criteri RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    from first administration of study intervention up to study end
    dalla prima somministrazione dell’intervento dello studio fino al termine dello studio
    E.5.2Secondary end point(s)
    1.DOR according to RECIST 1.1 assessed by an IRC
    2.Durable response of at least 6 months assessed by an IRC
    3.PFS according to RECIST 1.1 assessed by an IRC
    4.Objective response, DOR, DRR, and PFS according to RECIST 1.1 as assessed by the Investigator
    5.OS
    6.Occurrence of TEAEs and treatment-related AEs including AEs of special interest
    7.PK (pharmacokinetic) parameters for bintrafusp alfa
    8.Immunogenicity of bintrafusp alfa as measured by ADA assay
    1. DOR valutata da un IRC secondo i criteri RECIST 1.1
    2. Risposta durevole di almeno 6 mesi valutata da un IRC
    3. PFS valutata da un IRC secondo i criteri RECIST 1.1
    4. Risposta obiettiva, DOR, DRR e PFS valutati dallo sperimentatore secondo i criteri
    RECIST 1.1. 5. OS
    6. Insorgenza di TEAE ed EA correlati al trattamento, compresi EA di particolare
    interesse
    7. Parametri farmacocinetici (PK) di bintrafusp alfa
    8. Immunogenicità di bintrafusp alfa, come misurata mediante il saggio degli ADA
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-2-3-4.from first documentation of objective response to the date of first documentation of objective PD or death due to any cause
    5.from first administration of study intervention to the date of death due to any cause
    6.from first dose to final assessment up to approximately 2 years
    7.From first assessment up to 28 days after last treatment
    8.Time from first administration of treatment intervention to planned final assessment at approximately 2 years.
    1-2-3-4. dalla prima documentazione di risposta obiettiva alla data della prima
    documentazione di PD obiettiva o al decesso per qualsiasi causa
    5. dalla prima somministrazione dell’intervento in studio alla data del decesso per
    qualsiasi causa
    6. dalla prima dose alla valutazione finale fino a circa 2 anni
    7. dalla prima valutazione fino a 28 giorni dopo l’ultimo trattamento
    8. Intervallo di tempo compreso tra la prima somministrazione dell’intervento
    terapeutico alla valutazione finale programmata a circa 2 anni.
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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) 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 Yes
    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 No
    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 EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    France
    Italy
    Russian Federation
    Spain
    United States
    E.8.7Trial has a data monitoring committee No
    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
    The end of the study is defined as the date of completion of 24 months of follow-up after the accrual of the last participant. After the stipulated end of study, Survival Follow-up may continue until the last participant has died or at the discretion of the Sponsor.
    La fine dello studio è definita come la data del completamento di 24 mesi di follow-up dopo il reclutamento dell’ultimo partecipante. Dopo la fine dello studio stabilita, il follow-up della sopravvivenza potrà continuare fino al decesso dell’ultimo partecipante o a discrezione dello sponsor.
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 26
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 3
    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 state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 19
    F.4.2.2In the whole clinical trial 29
    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 a participant has completed the study, has withdrawn consent, or has been withdrawn early, symptom guided appropriate treatment will be administered, if required, in accordance with the study site’s standard of care and generally accepted medical practice and depending on the participant’s individual medical needs. Participants will be followed for survival and AEs.
    On withdrawal from the study, participants may receive whatever care they and their physicians agree upon.
    Dopo che un partecip avrà completato lo studio, avrà ritirato il consenso o si sarà ritirato anticipatam, se necessario, verrà somministrato un trattam appropriato in base ai sintomi, in conformità con lo standard di cura del centro e con la pratica medica comunemente accettata e a seconda delle necessità mediche individuali del partecip.I partecip saranno seguiti per la sopravvivenza e gli EA. Al momento del ritiro dallo studio,i partecip possono ricevere la cura concordata con i propri medici.
    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 Decision2020-10-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-07-08
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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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
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