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    Summary
    EudraCT Number:2020-005386-13
    Sponsor's Protocol Code Number:ARC-9
    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:2021-06-07
    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 number2020-005386-13
    A.3Full title of the trial
    A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients with Metastatic Colorectal Cancer
    Studio piattaforma di fase 1B/2, in aperto, randomizzato per valutare l’efficacia e la sicurezza delle combinazioni di trattamento basate su AB928 in pazienti affetti da tumore del colon-retto metastatico.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study Evaluating the Efficacy and Safety of AB928-Based Treatment
    Combinations in Patients with Metastatic Colorectal Cancer
    Uno studio che valuta l'efficacia e la sicurezza del trattamento basato su AB928
    Combinazioni in pazienti con carcinoma colorettale metastatico
    A.3.2Name or abbreviated title of the trial where available
    ARC-9
    ARC-9
    A.4.1Sponsor's protocol code numberARC-9
    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 SponsorArcus Biosciences 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 supportARCUS BIOSCIENCES INC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationArcus Biosciences, Inc
    B.5.2Functional name of contact pointClinical Trial Inquiry
    B.5.3 Address:
    B.5.3.1Street Address3928 Point Eden Way, Hayward CA 94545 United States
    B.5.3.2Town/ cityCalifornia
    B.5.3.3Post code94545
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrialinquiry@arcusbio.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 nameZimberelimab
    D.3.2Product code [AB122]
    D.3.4Pharmaceutical form Concentrate for solution for injection/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 INNZimberelimab
    D.3.9.2Current sponsor codeAB122
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 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 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 nameEtrumadenant
    D.3.2Product code [AB928]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEtrumadenant
    D.3.9.2Current sponsor codeAB928
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 nameAB680
    D.3.2Product code [AB680]
    D.3.4Pharmaceutical form Powder and solvent for solution for injection/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 INNAB680
    D.3.9.2Current sponsor codeAB680
    D.3.9.4EV Substance CodeSUB218819
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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
    Metastatic colorectal cancer
    Tumore metastatico del colon retto
    E.1.1.1Medical condition in easily understood language
    Metastatic colorectal cancer
    Tumore metastatico del colon retto
    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 10052362
    E.1.2Term Metastatic colorectal cancer
    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
    • Cohorts A (2L), B (3L), and C (>3L)
    - Efficacy: To evaluate the antitumor activity of etruma-based treatment
    combinations
    • All Cohorts (including Safety Run-in Cohort)
    - Safety: To evaluate the safety and tolerability of entruma-based treatement combinations
    • Coorti A (2L), B (3L) e C (>3L)
    Efficacia: valutare l’attività antitumorale delle combinazioni di trattamento basate su etruma.
    • Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    - Sicurezza: valutare la sicurezza e la tollerabilità delle combinazioni di trattamento basate su etruma.
    E.2.2Secondary objectives of the trial
    • Cohorts A (2L), B (3L), and C (>3L)
    - To evaluate clinical activity of etruma-based treatment combinations
    • All Cohorts (including Safety Run-in Cohort)
    - To determine the pharmacokinetic (PK) profile for components of
    etruma-based treatment combinations
    • All Cohorts (including Safety Run-in Cohort)
    - To assess immunogenicity of the biologic component(s) of
    combination therapy where appropriate
    • Coorti A (2L), B (3L) e C (>3L)
    - Valutare l’attività clinica delle combinazioni di trattamento basate su etruma.
    • Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    - Determinare il profilo farmacocinetico (PK) dei componenti delle combinazioni di trattamento basate su etruma.
    • Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    - Valutare l’immunogenicità del/i componente/i biologico/i della terapia in combinazione, se appropriato
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this
    protocol2.Male and female participants =18 years of age inclusive, at the time of
    signing the informed consent
    3.Ability to comply with the study protocol in the Investigator's judgment
    4.Histologically confirmed metastatic colorectal adenocarcinoma
    5.Measurable (at least one target lesion) disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation. Note: Inclusion Criterion 5 is not required for participants entering into the Safety Run-in Cohort.
    6.Participants with measurable disease and accessible tumor will undergo a pre-treatment biopsy (unless an archived specimen is
    available) and on-treatment fresh tumor biopsy. The biopsy must not put participants at undue risk and the procedure must not be more invasive
    than a core biopsy as documented in the medical record by the Investigator. Fresh biopsy of a tumor lesion not previously irradiated should be obtained. Tumors progressing in a prior site of radiation may be considered after Sponsor consultation.
    • Participants for biopsy should have at least two measurable lesions at
    baseline: one for tissue sampling and one for radiographic response
    assessment.
    7.Eastern Cooperative Oncology Group (ECOG) performance status of 0
    or 1.
    8.Life expectancy =3 months as determined by the Investigator
    9.Adequate hematologic and end-organ function defined by the following laboratory test results at screening:
    a. Absolute neutrophil count =1.5 x 10^9/L (1500/µL) without granulocyte colony-stimulating factor support
    b. White blood cell counts =2.5x 10^9/L (2500/µL)
    c. Lymphocyte count =0.5 x 10^9/L (500/µL)
    d. Platelet count =100 x 10^9/L (100,000/µL) without transfusion
    e. Hemoglobin =90 g/L (9.0 g/dL)
    Participants must not have been transfused within 2 weeks prior to screening to meet minimum platelet and hemoglobin parameters.
    f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
    =2.5 x upper limit of normal (ULN), with the following exception:
    i. Participants with documented liver metastases: AST and ALT =5 x ULN
    ii. Participants with documented liver or bone metastases: alkaline
    phosphatase (ALP) =5 x ULN
    g. ALP =5 x ULN
    i. If ALP >5 × ULN, then gamma-glutamyl transpeptidase must be within normal limits
    h. Total bilirubin =1.5 x ULN, with the following exception:
    i. Participants with known Gilbert syndrome: serum bilirubin level =3 x
    ULN
    i. Albumin =25 g/L (2.5 g/dL)
    j. Serum creatinine =1.5 x ULN or creatinine clearance =30 mL/min as
    determined by Cockcroft-Gault equation (Cockcroft and Gault, 1976)
    10.Negative human immunodeficiency virus (HIV) test at screening. Due
    to safety concerns related to viral activation, development of a
    secondary malignancy, as well as the potential for increased treatment
    related toxicity, eligible participants must not have evidence of chronic
    HIV infection at screening
    11.Negative hepatitis B surface antigen (HBsAg) and core antibody
    (HBcAb) tests, or positive total HBcAb test followed by a negative
    hepatitis B virus (HBV) DNA test at screening. The HBV test will be
    performed only for participants who have a positive total HBcAb test.
    Due to safety concerns related to viral activation, development of a
    secondary malignancy, as well as the potential for increased treatment
    related toxicity, eligible participants must not have evidence of chronic
    viral hepatitis infection at screening
    12.Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening.
    13.Agreement to remain abstinent
    Due to limited space, for Study Treatment-Specific Inclusion Criteria
    please refer to section 7.2 of the protocol
    1.Capacità di fornire un consenso informato firmato in conformità ai requisiti e alle restrizioni elencati nell'ICF e nel presente protocollo.
    2.Soggetti partecipanti di sesso maschile e femminile di età =18 anni al momento della firma del consenso informato.
    3.Capacità di conformarsi al protocollo di studio a giudizio dello Sperimentatore.
    4.Adenocarcinoma metastatico del colon-retto confermato con esame istologico.
    5.Patologia quantificabile (almeno una lesione bersaglio) secondo i criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1. Le lesioni precedentemente irradiate possono essere considerate una patologia quantificabile solo se, dopo le radiazioni, è stata inequivocabilmente documentata la progressione della malattia in quell’area.
    Nota: Il criterio di inclusione 5 non è richiesto per i partecipanti reclutati nella Coorte del periodo preliminare per la sicurezza.
    6.I partecipanti con patologia quantificabile e tumore accessibile saranno sottoposti a una biopsia prima del trattamento (a meno che non sia disponibile un campione archiviato) e a una biopsia del tumore fresco durante il trattamento. La biopsia non deve mettere i partecipanti a rischio eccessivo e la procedura non deve essere più invasiva di una biopsia percutanea come documentato nella cartella clinica dallo Sperimentatore. Occorre una recente biopsia di una lesione tumorale non irradiata in precedenza. I tumori in fase di progressione in un’area precedentemente sottoposta alla radiazione possono essere considerati dopo aver consultato lo Sponsor.
    • I partecipanti alla biopsia devono avere almeno due lesioni valutabili al basale: una per il campionamento dei tessuti e una per la valutazione radiografica della risposta.
    7.Performance status ECOG (Eastern Cooperative Oncology Group) tra 0 e 1.
    8.Aspettativa di vita =3 mesi come determinato dallo Sperimentatore.
    9.Adeguata funzione ematologica e di organo terminale definita dai seguenti risultati agli esami di laboratorio allo screening:
    a. Conta assoluta dei neutrofili =1,5 × 109/l (1500/µl) senza supporto del fattore di stimolazione della colonia dei granulociti,
    b. Conte dei globuli bianchi =2,5 × 109/l (2500/µl),
    c. Conta dei linfociti =0,5 × 109/l (500/µl),
    d. Conta delle piastrine =100 × 109/l (100.000/µl) senza trasfusione,
    e. Emoglobina =90 g/l (9.0 g/dl).
    I partecipanti non devono essere stati sottoposti a trasfusione nelle 2 settimane precedenti lo screening per soddisfare i parametri minimi delle piastrine e dell’emoglobina.
    f. Aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT)
    =2,5 x limite superiore della norma (ULN), con la seguente eccezione:
    i. Partecipanti con metastasi epatiche documentate: AST e ALT =5 x ULN
    ii. Partecipanti con metastasi epatiche o ossee documentate: fosfatasi alcalina (ALP) =5 x ULN
    g. ALP =5 x ULN
    i. Se ALP >5 x ULN, la gamma-glutamiltranspeptidasi deve rientrare nei limiti normali
    h. Bilirubina totale =1,5 x ULN, con la seguente eccezione:
    i. Partecipanti con sindrome di Gilbert nota: livello di bilirubina nel siero =3 x ULN
    i. Albumina =25 g/l (2,5 g/dl)
    j. Creatinina serica =1,5 x ULN o clearance della creatinina =30 ml/min come determinato dall'equazione di Cockcroft-Gault (Cockcroft e Gault, 1976).
    10.Test negativo del virus dell'immunodeficienza umana (HIV) allo screening. Per motivi di sicurezza connessi all'attivazione virale, allo sviluppo di tumori maligni secondari e al potenziale aumento della tossicità correlata al trattamento, i partecipanti idonei non devono mostrare infezione da HIV cronica allo screening.
    A causa dello spazio limitato, per i criteri di inclusione specifici per il trattamento dello studio fare riferimento alla sezione 7.2 del protocollo
    E.4Principal exclusion criteria
    approved agents, systemic radiotherapy, or investigational therapy,
    within 4 weeks (or 5 half-lives) whichever is shorter prior to initiation of
    study treatment. Prior focal radiotherapy must be completed at least 2
    weeks prior to the initiation of study treatment
    2.QTc =480 msec using Fredericia's QT correction formula (based on an
    average of triplicate recordings)
    3.Prior allogeneic stem cell or solid organ transplantation
    4.Treatment with systemic immunostimulatory agents (including, but
    not limited to, interferon and interleukin-2) within 4 weeks (or 5 halflives)
    whichever is shorter prior to initiation of study treatment
    5.Treatment with systemic immunosuppressive medication (including,
    but not limited to, corticosteroids, cyclophosphamide, azathioprine,
    methotrexate, thalidomide, and antitumor necrosis factor-a agents)
    administered at >10 mg/day prednisone or equivalent within 2 weeks
    prior to initiation of study treatment, or anticipation of need for systemic
    immunosuppressant medication during study treatment, with the
    following exceptions:
    a. Participants who received low dose (=10 mg/day prednisone or
    equivalent), systemic immunosuppressant medications or a one-time
    pulse dose of systemic immunosuppressant medication (eg, 48 hours of
    corticosteroids for a contrast allergy) are eligible for the study after
    Medical Monitor approval has been obtained.
    b. Participants who received mineralocorticoids (eg, fludrocortisone),
    inhaled or intranasal corticosteroids for chronic obstructive pulmonary
    disease or asthma, or low dose corticosteroids for orthostatic
    hypotension or adrenal insufficiency are eligible for the study after
    Medical Monitor approval has been obtained.
    6.Treatment with a live, attenuated vaccine within 4 weeks prior to
    initiation of study treatment, or anticipation of need for such a vaccine
    during study treatment or within 5 months after the last dose of study
    treatment
    7.Current treatment with anti-viral therapy for HBV
    8.Structurally unstable bone lesions suggesting impending fracture
    9.Symptomatic, untreated, or actively progressing central nervous
    system (CNS) metastases
    Due to limited space, for Study Treatment-Specific Inclusion Criteria
    please refer to relative section of the protocol
    1.Trattamento antitumorale precedente per la patologia in esame, con farmaci approvati, radioterapia sistemica o terapia sperimentale, nelle 4 settimane (o 5 emivite, a seconda di quale periodo sia più breve) precedenti l'inizio del trattamento dello studio. La radioterapia focale precedente deve essere stata completata almeno 2 settimane prima dell'inizio del trattamento in studio.
    2.Qtc =480 msec usando la formula di correzione QT di Fredericia (basata su una media di registrazioni in triplicato).
    3.Precedente trapianto di cellule staminali allogeniche o di organi solidi.
    4.Trattamento con agenti immunostimolanti sistemici (compresi, a titolo esemplificativo ma non esaustivo, interferone e interleuchina-2) nelle 4 settimane (o 5 emivite, a seconda di quale periodo sia più breve) precedenti l'inizio del trattamento dello studio.
    5.Trattamento con farmaci immunosoppressori sistemici (compresi, a titolo esemplificativo ma non esaustivo, corticosteroidi, ciclofosfamide, azatioprina, metotrexato, talidomide e agenti del fattore a di necrosi antitumorale) somministrati a >10 mg/giorno di prednisone o equivalente nelle 2 settimane precedenti l'inizio del trattamento dello studio, o previsione della necessità di farmaci immunosoppressori sistemici durante il trattamento dello studio, con le seguenti eccezioni:
    a. Partecipanti che hanno ricevuto una dose bassa (=10 mg/giorno prednisone o equivalente) di farmaci immunosoppressori sistemici o una dose una tantum di farmaci immunosoppressori sistemici (ad esempio, 48 ore di corticosteroidi per un'allergia da mezzo di contrasto) sono idonei allo studio dopo aver ottenuto l'approvazione del responsabile del monitoraggio medico.
    b. Partecipanti che hanno ricevuto mineralocorticoidi (ad esempio, fludrocortisone), corticosteroidi inalati o intranasali per broncopneumopatia ostruttiva cronica o asma, o corticosteroidi a basso dosaggio per ipotensione ortostatica o insufficienza surrenale sono idonei allo studio dopo aver ottenuto l'approvazione del responsabile del monitoraggio medico.
    6.Trattamento con vaccino vivo attenuato nelle 4 settimane precedenti l'inizio del trattamento dello studio o previsione della necessità di tale vaccino durante il trattamento dello studio o nei 5 mesi successivi all'ultima dose di trattamento dello studio.
    7.Trattamento in corso con terapia antivirale per HBV.
    8.Lesioni ossee strutturalmente instabili che suggeriscono una frattura imminente.
    9.Metastasi del sistema nervoso centrale (SNC) sintomatiche, non trattate o in fase di progressione attiva.
    A causa dello spazio limitato, per i criteri di inclusione specifici per il trattamento dello studio fare riferimento alla sezione corrispondente del protocollo
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy:
    Cohort A (2nd line [2L])
    • Progression-free survival (PFS) according to Response Evaluation
    Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
    Cohort B (3rd line [3L]) (Co-primary)
    • PFS according to RECIST v1.1 as assessed by the Investigator
    • Overall survival (OS)
    Cohort C (>3 lines [>3L])
    • Objective response rate (ORR) according to RECIST v1.1, as assessed
    by the Investigator
    Safety:
    All Cohorts (including Safety Run-in Cohort)
    • Incidence and severity of adverse events (AEs) and serious adverse
    events (SAEs)
    Efficacia:
    Coorte A (seconda linea )
    • Sopravvivenza libera dalla malattia (PFS) secondo i criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1, in base alla valutazione dello Sperimentatore della Coorte B (terza linea ) (Co-primaria)
    • PFS secondo i RECIST v1.1, in base alla valutazione dello Sperimentatore
    • OS
    Coorte C (>3 linee [>3L])
    • Tasso di risposta obiettiva (ORR) secondo i RECIST v1.1, in base alla valutazione dello Sperimentatore

    Sicurezza:
    Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    • Incidenza e gravità degli eventi avversi (AE) e degli eventi avversi gravi (SAE)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Efficacy:
    Cohort A (2nd line [2L]): PFS
    Defined as the time from treatment assignment until first documentation
    of progressive disease or death, whichever occurs first.
    Cohort B (3rd line [3L]) (Co-primary): PFS and OS
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    PFS (defined above) and OS, defined as the time from treatment
    assignment until death due to any cause.
    Cohort C (>3 lines [>3L]): ORR
    Defined as the proportion of participants with a best overall response of
    CR or PR according to RECIST v1.1
    Safety:
    Throughout the trial
    Efficacia:
    Coorte A (seconda linea ): PFS
    Tempo intercorrente tra l'assegnazione del trattamento e la prima documentazione di progressione della malattia o decesso, a seconda di quale si verifichi prima.
    Coorte B (terza linea ) (Co-primaria): PFS e OS PFS (definita sopra) e OS definita come il tempo intercorrente dall’assegnazione del
    trattamento fino al decesso per qualsiasi causa.
    Coorte C (>3 linee [>3L]): ORR
    Percentuale di partecipanti con la migliore OR di risposta completa (CR) o parziale (PR) secondo i RECIST v1.1

    Sicurezza:
    Durante la sperimentazione
    E.5.2Secondary end point(s)
    Cohort A (2L)
    • ORR according to RECIST v1.1, as assessed by the Investigator,
    duration of response (DoR; defined as the time from first documentation
    of disease response [complete response (CR) or partial response (PR)]
    until first documentation of confirmed progressive disease), disease
    control rate (DCR; defined as CR, PR, or stable disease [SD] for >12
    weeks), and OS
    Cohort B (3L)
    • ORR, DoR, and DCR (CR, PR, or SD for >12 weeks) according to RECIST
    v1.1, as assessed by the Investigator.
    Cohort C (>3L)
    • DoR and DCR (CR, PR, or SD for >12 weeks) according to RECIST v1.1,
    as assessed by the Investigator
    All Cohorts (including Safety Run-in Cohort)
    • Serum/plasma concentration and PK parameters for components of
    etruma-based combination therapy
    All Cohorts (including Safety Run-in Cohort)
    • Number and percentage of participants who develop antidrug
    antibodies (ADAs) to the biologic component(s) of combination therapy
    Coorte A (2L)
    • ORR secondo i RECIST v1.1, in base alla valutazione dello Sperimentatore, durata della risposta (DoR; definita come il periodo di tempo che intercorre dalla prima documentazione di risposta della malattia fino alla prima documentazione di progressione confermata della malattia), tasso di controllo della malattia (DCR; definito come CR, PR o malattia stabile per >12 settimane) e OS
    Coorte B (3L)
    • ORR, DoR e DCR (CR, PR o SD per >12 settimane) secondo i RECIST v1.1, in base alla valutazione dello Sperimentatore.
    Coorte C (>3L)
    • DoR e DCR (CR, PR o SD per >12 settimane) secondo i RECIST v1.1, in base alla valutazione dello Sperimentatore
    Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    • Concentrazione nel siero/plasma e parametri PK per i componenti della terapia in combinazione basata su etruma
    Tutte le coorti (inclusa la coorte del periodo preliminare per la sicurezza)
    - • Numero e percentuale di partecipanti che sviluppano anticorpi antifarmaco (ADAs) al/i componente/i biologico/i della terapia in combinazione
    E.5.2.1Timepoint(s) of evaluation of this end point
    Cohort A (2L):
    ORR Defined as the proportion of participants with a best overall
    response of CR or PR according to RECIST v1.1.
    DoR defined as the time from first documentation of disease response
    (CR or PR) until first documentation of confirmed progressive disease.
    DCR defined as the proportion of participants with a best overall
    response of CR, PR, or SD. The duration of time required for a participant
    with SD to be considered in disease control is >12 weeks.
    OS Defined as the time from treatment assignment until death due to
    any cause.
    • Cohort B (3L): ORR, DoR, and DCR (as defined above)
    • Cohort C (>3L): DoR and DCR (as defined above)
    All cohorts
    Throughout the trial
    Coorte A (2L):
    ORR definita come la percentuale di partecipanti con la migliore OR di CR o PR secondo i RECIST v1.1.
    DoR definita come il tempo intercorrente dalla prima documentazione della risposta alla malattia (CR o PR) fino alla prima documentazione di progressione confermata della malattia.
    DCR definita come la percentuale di partecipanti con la migliore OR di CR, PR o SD. La durata del controllo della malattia da considerare per un partecipante con SD è >12 settimane.
    OS definita come il tempo intercorrente dall’assegnazione dell trattamento fino al decesso per qualsiasi causa.
    • Coorte B (3L): ORR, DoR e DCR (come definite sopra)
    • Coorte C (>3L): DoR e DCR (come definite sopra)
    Tutte le coorti durante la sperimentazione
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    Immunogenicità
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations
    Studio di valutazione dell'efficacia e della sicurezza del trattamento basato su AB928 Combinazioni
    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 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 No
    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 trial6
    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 EEA36
    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
    France
    Germany
    Italy
    Korea, Democratic People's Republic of
    Singapore
    Spain
    United Kingdom
    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
    LPLV
    Ultimo paziente ultima visita LPLV
    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 days0
    E.8.9.2In all countries concerned by the trial years2
    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: 2210
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 37
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 143
    F.4.2.2In the whole clinical trial 247
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Nesuno
    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 Decision2021-06-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-02-15
    P. End of Trial
    P.End of Trial StatusOngoing
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