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   38177   clinical trials with a EudraCT protocol, of which   6271   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:2018-000265-37
    Sponsor's Protocol Code Number:BGB-900-101
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-11-16
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2018-000265-37
    A.3Full title of the trial
    Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-L1 Monoclonal Antibody BGB-A333 Alone and in Combination with Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients with Advanced Solid Tumors
    Estudio en fase I-II para investigar la seguridad, la tolerabilidad, la farmacocinética y la actividad antitumoral preliminar del anticuerpo monoclonal anti-PD-L1 BGB-A333 en monoterapia y en combinación con el anticuerpo monoclonal anti-PD-1 tislelizumab en pacientes con tumores sólidos avanzados
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 1-2 Study Investigating Safety, Tolerability, how the drug will be accepted in the body with treatment of BGB-A333 Alone and in Combination with Tislelizumab in Patients with Malignant Tumors
    Estudio en fase I-II para investigar la seguridad, la tolerabilidad, cómo se aceptará el fármaco en el cuerpo con el tratamiento de BGB-A333 solo y en combinación con tislelizumab en pacientes con tumores malignos
    A.4.1Sponsor's protocol code numberBGB-900-101
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03379259
    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 SponsorBeiGene, Ltd.
    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 supportBeiGene Ltd.,
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBeiGene Ltd.
    B.5.2Functional name of contact pointBeiGene Clinical support
    B.5.3 Address:
    B.5.3.1Street Addressc/o BeiGene USA Inc., 1900 Powell Street, Suite 500
    B.5.3.2Town/ cityEmeryville
    B.5.3.3Post code94608
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34620 423 957
    B.5.6E-mailBeiGeneClinicalSupportUS@beigene.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.3.2Product code BGB-A333
    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 INNNot assigned yet
    D.3.9.1CAS number Not assigned
    D.3.9.2Current sponsor codeBGB-A333
    D.3.9.3Other descriptive namePRD6540951
    D.3.9.4EV Substance CodeSUB193627
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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 No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTislelizumab
    D.3.2Product code BGB-A317
    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 INNtislelizumab
    D.3.9.1CAS number 1858168-59-8
    D.3.9.2Current sponsor codeBGB-A317
    D.3.9.4EV Substance CodeSUB189550
    D.3.10 Strength
    D.3.10.1Concentration unit mg/l milligram(s)/litre
    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 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
    Anti-PD-L1 Monoclonal Antibody BGB-A333 Alone and in Combination with Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients with Advanced Solid Tumors
    El anticuerpo monoclonal anti-PD-L1 BGB-A333 en monoterapia y en combinación con el anticuerpo monoclonal anti-PD-1 tislelizumab en pacientes con tumores sólidos avanzados
    E.1.1.1Medical condition in easily understood language
    BGB-A333 Alone and in Combination with Tislelizumab (BGB-A317) in Patients with Advanced Solid Tumors
    BGB-A333 solo y en combinación con tislelizumab en pacientes con tumores sólidos avanzados
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10065143
    E.1.2Term Malignant solid tumour
    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
    1) For Phase 1:
    • To assess the safety and tolerability of BGB-A333 alone and in combination with tislelizumab in patients with advanced solid tumors
    • To determine the MTD, if any, and RP2D for BGB-A333 alone and in combination with tislelizumab

    2) For Phase 2: To assess ORR per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of BGB-A333 alone and in combination with tislelizumab in patients with selected tumor types
    1) Para fase 1:
    - Evaluar la seguridad y tolerabilidad de BGB-A333 en monoterapia y en combinación con tislelizumab (BGB-A317) en pacientes con tumores sólidos avanzados.
    - Determinar la dosis máxima tolerada (DMT), si la hubiera, y la dosis recomendada para la fase 2 (DRF2) para BGB-A333 en monoterapia y en combinación con tislelizumab.

    2)Para fase 2:
    -Evaluar la TRO según los Criterios de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1, de BGB-A333 en monoterapia y en combinación con tislelizumab en pacientes con tipos seleccionados de tumor.
    E.2.2Secondary objectives of the trial
    1) For Phase 1:
    • To assess the preliminary antitumor activity of BGB-A333 alone and in combination with tislelizumab
    • To characterize the PK of BGB-A333 alone and in combination with tislelizumab
    • To assess host immunogenicity to BGB-A333 alone and in combination with tislelizumab

    2) For Phase 2:
    • To assess other tumor assessment outcomes (ie, duration of response [DOR], progression-free survival [PFS], and disease control rate [DCR]) per RECIST v1.1
    • To characterize safety and tolerability of BGB-A333 alone and in combination with tislelizumab
    • To characterize the PK of BGB-A333 alone and in combination with tislelizumab
    • To assess host immunogenicity to BGB-A333 and tislelizumab
    1) Para fase 1:
    - Evaluar la actividad antitumoral preliminar de BGB-A333 en monoterapia y en combinación con tislelizumab.
    - Caracterizar la farmacocinética (FC) de BGB-A333 en monoterapia y en combinación con tislelizumab.
    - Evaluar la inmunogenicidad del hospedador frente a BGB-A333 en monoterapia y en combinación con tislelizumab.

    2)Para fase 2:
    - Evaluar otras variables de evaluación del tumor, es decir, duración de la respuesta (DR), supervivencia sin progresión (SSP) y tasa de control de la enfermedad (TCE), según RECIST versión 1.1.
    - Caracterizar la seguridad y la tolerabilidad de BGB-A333 en monoterapia y en combinación con tislelizumab.
    - Caracterizar la FC de BGB-A333 en monoterapia y en combinación con tislelizumab.
    - Evaluar la inmunogenicidad del hospedador frente a BGB-A333 y tislelizumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able to provide written informed consent and can understand and comply with the requirements of the study
    2. Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
    3. For Phase 1 only: patients with histologically or cytologically confirmed advanced or metastatic, unresectable solid tumors who have progressed during or after standard therapy or for which treatment is not available, not tolerated or refused

    4. For Phase 2 only:
    a. Arm 1: Patients with locally advanced and metastatic urothelial carcinoma who have progressed during or after treatment with platinum-based chemotherapy or who could not tolerate platinum-based chemotherapy.
    b. Sponsor may consider other tumor types including but not limited to NSCLC, RCC, SCCHN, GC, MSI-high cancer, etc. The eligibility criteria for patients with these tumor types will be defined in future protocol amendments

    5. Patient must have at least one measurable lesion as defined per RECIST v1.1
    Note: The target lesion(s) selected have not been previously treated with local therapy or the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST v1.1.
    6. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
    7. Has adequate organ function as indicated by the following laboratory values:
    a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 75 × 109/L, hemoglobin ≥ 90 g/L. Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
    b. Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated GFR ≥ 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 7)
    c. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN
    d. Serum total bilirubin ≤ 1.5 X ULN (total bilirubin must be < 3 X ULN for patients with Gilberts syndrome)
    e. For hepatocellular carcinoma (HCC) patients only, patient must meet the Child-Pugh A classification for liver function as assessed within 7 days before the first dose of study drug(s) (Appendix 11).
    8. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug (s), and have a negative urine or serum pregnancy test ≤ 7 days of the first dose of study drug(s)
    9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)
    1. Ser capaz de proporcionar consentimiento informado por escrito y poder entender y cumplir los requisitos del estudio.
    2. Edad ≥18 años el día de la firma del FCI (o la edad legal de consentimiento de la jurisdicción en la que tenga lugar el estudio).
    3. Solo para la fase 1: pacientes con tumores sólidos irresecables, avanzados o metastásicos, confirmados histológica o citológicamente, que hayan progresado durante o después del tratamiento estándar o para los cuales no haya disponible tratamiento o bien no se tolere o se rechace.

    4. Solo para la fase 2:
    a. Grupo 1: pacientes con carcinoma urotelial (CU) localmente avanzado y metastásico que hayan progresado durante o después del tratamiento con quimioterapia basada en platino o que no podían tolerarla.
    b. El promotor podría considerar otros tipos de tumores, como el CPNM, CCR, CECC, CG, cáncer con IMS-alta, etc. Los criterios de aptitud para los pacientes con estos tipos de tumores se definirán en futuras enmiendas al protocolo.

    5. El paciente debe tener al menos una lesión mensurable, según lo define RECIST v1.1.
    Nota: la lesión o lesiones diana seleccionadas no han sido tratadas previamente con tratamiento local o bien la lesión o lesiones diana seleccionadas que se encuentran dentro del campo de tratamiento local previo han progresado posteriormente según lo define RECIST v1.1.
    6. Tiene un estado general ≤1 según el Grupo Oncológico Cooperativo del Este (ECOG).
    7. Presenta una función orgánica adecuada, según determinación mediante los siguientes valores analíticos:
    a. Recuento absoluto de neutrófilos (RAN) ≥1,5 × 109/l, trombocitos ≥75 x 109/l, hemoglobina ≥90 g/l. Nota: los pacientes no deben haber necesitado una transfusión de sangre o apoyo con factor de crecimiento ≤14 días antes de la obtención de la muestra.
    b. Creatinina sérica ≤1,5 × límite superior de la normalidad (LSN) o TFG estimada ≥60 ml/min/1,73 m2 según la ecuación de la colaboración epidemiológica para la enfermedad renal crónica (Apéndice 7).
    c. Aspartato transaminasa (AST) y alanina aminotransferasa (ALT) ≤3 × LSN
    d. Bilirrubina sérica total ≤1,5 x LSN (la bilirrubina total debe ser <3 x LSN para los pacientes con síndrome de Gilbert).
    e. Solo para los pacientes con carcinoma hepatocelular (CHC), el paciente debe cumplir la clasificación de la clase A de Child-Pugh para la función hepática, evaluada en el plazo de 7 días antes de la primera dosis de fármaco(s) del estudio (Apéndice 11).
    8. Las mujeres con capacidad de concebir deben estar dispuestas a usar un método anticonceptivo de gran efectividad durante todo el estudio y ≥120 días después de la última dosis de fármaco(s) del estudio, y tener un resultado negativo en la prueba de embarazo en orina o suero ≤7 días antes de la primera dosis de fármaco(s) del estudio.
    9. Los hombres que no sean estériles deben estar dispuestos a usar un método anticonceptivo de gran efectividad durante todo el estudio y ≥120 días después de la última dosis de fármaco(s) del estudio.
    E.4Principal exclusion criteria
    1. Active leptomeningeal disease or uncontrolled brain metastasis. Patients with equivocal findings or with confirmed brain metastases are eligible for enrollment provided they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s).
    2. Active autoimmune diseases or history of autoimmune diseases that may relapse
    Note: Patients with the following diseases are not excluded and may proceed to further screening:
    a. Controlled type 1 diabetes
    b. Hypothyroidism (provided it is managed with hormone replacement therapy only)
    c. Controlled celiac disease
    d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
    e. Any other disease that is not expected to recur in the absence of external triggering factors
    3. Any active malignancy ≤ 2 years before the first dose of study drug(s), except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
    4. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before administration of study drug
    Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:
    a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
    b. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
    c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
    5. With uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management
    6. With significant pulmonary disease (ie, chronic obstructive pulmonary disease [COPD], emphysema or chronic bronchitis) or with history of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
    7. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. Note: antiviral therapy is permitted for patients with hepatocellular carcinoma
    8. A known history of HIV infection
    9. A known history of HBV or HCV infection, except for patients with HCC
    19. Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways)
    1. Enfermedad leptomeníngea activa o metástasis cerebral sin controlar. Los pacientes con resultados dudosos o con metástasis cerebrales confirmadas son aptos para la inscripción, siempre que sean asintomáticos y radiológicamente estables sin necesidad de tratamiento con corticoesteroides durante al menos 4 semanas antes de la primera dosis de fármaco(s) del estudio.
    2. Enfermedades autoinmunitarias activas o antecedentes de enfermedades autoinmunitarias que pueden recidivar
    Nota: los pacientes con las siguientes enfermedades no están excluidos y podrán proceder con la selección:
    a. Diabetes tipo 1 controlada
    b. Hipotiroidismo (siempre y cuando se gestione solamente con tratamiento sustitutivo hormonal)
    c. Enfermedad celíaca controlada
    d. Enfermedades cutáneas que no requieran tratamiento sistémico (p. ej., vitiligo, psoriasis, alopecia)
    e. Cualquier otra enfermedad que no se espera que se repita en ausencia de factores de activación externos.
    3. Cualquier neoplasia maligna activa ≤2 años antes de la primera dosis de fármaco(s) del estudio, excepto para el cáncer específico que se investiga en este estudio y cualquier cáncer localmente recurrente que haya sido tratado de forma curativa (p. ej., cáncer de piel de células basales o escamosas resecado, cáncer superficial de vejiga, carcinoma localizado del cuello uterino o de mama).
    4. Cualquier afección que requiera tratamiento sistémico con corticoesteroides (>10 mg al día de prednisona o equivalente) o con otra medicación inmunodepresora ≤14 días antes de la administración de fármaco del estudio.
    Nota: los pacientes que actualmente estén, o hayan estado anteriormente, en tratamiento con alguno de los siguientes corticoides no están excluidos:
    a. Corticoides de sustitución suprarrenal (dosis ≤10 mg al día de prednisona o equivalente)
    b. Corticoesteroides tópicos, oculares, intrarticulares, intranasales o inhalados con absorción sistémica mínima
    c. Ciclo corto (≤7 días) de corticoesteroides recetados de forma profiláctica (p. ej., para la alergia a medios de contraste) o para el tratamiento de una afección no autoinmunitaria (p. ej., reacción de hipersensibilidad tardía provocada por un alérgeno de contacto)
    5. Con diabetes sin controlar o anomalías mayores de grado 1 en las pruebas analíticas para el potasio, sodio, o calcio corregido, a pesar del tratamiento médico estándar.
    6. Con enfermedad pulmonar significativa (es decir, enfermedad pulmonar obstructiva crónica [EPOC], enfisema o bronquitis crónica) o con antecedentes de enfermedad pulmonar intersticial, neumonitis no infecciosa o enfermedades sin controlar, incluida la fibrosis pulmonar, enfermedades pulmonares agudas, etc.
    7. Con infecciones graves crónicas o activas que requieran tratamiento sistémico antibacteriano, antifúngico o antivírico, incluida la infección de tuberculosis, etc. Nota: el tratamiento antivírico está permitido para los pacientes con carcinoma hepatocelular.
    8. Antecedentes conocidos de infección por VIH
    9. Antecedentes conocidos de infección por VHB o VHC, excepto para los pacientes con CHC
    19. Recibió terapia previa con un anticuerpo anti-PD-1, anti-PD-L1, anti-PD-L2 o anti-CTLA-4 (o cualquier otro anticuerpo dirigido a las vías de coestimulación de células T)
    E.5 End points
    E.5.1Primary end point(s)
    1) For Phase 1:
    • Safety and tolerability: The safety of BGB-A333 alone and in combination with tislelizumab will be assessed throughout the study by monitoring AEs and SAEs per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE Version 4.03, relevant physical examination, electrocardiograms (ECGs) and laboratory assessments as needed
    • The MTD, if any, and RP2D for BGB-A333 alone and in combination with tislelizumab will be determined based on safety, tolerability, PK, preliminary efficacy, and other available data

    2) For Phase 2:
    Efficacy evaluations: ORR will be determined by investigators based on RECIST version 1.1. The ORR is defined as the proportion of patients who had confirmed CR or PR assessed by investigator using RECIST version 1.1. ORR and its 95% CI will be summarized in the Safety Population and Efficacy Evaluable Population
    1) Para fase 1:
    - Seguridad y tolerabilidad: se evaluará la seguridad de BGB-A333 en monoterapia y en combinación con tislelizumab durante todo el estudio vigilando los AA y los AAG, conforme a los Criterios terminológicos comunes para acontecimientos adversos del Instituto Nacional del Cáncer (NCI-CTCAE), versión 4.03, mediante una exploración física pertinente, electrocardiogramas y evaluaciones analíticas, según sea necesario.
    - La DMT, si la hubiera, y la DRF2 para BGB-A333 en monoterapia y en combinación con tislelizumab se determinarán basándose en la seguridad, tolerabilidad, FC, eficacia preliminar y otros datos disponibles

    2) Para la fase 2:
    - Evaluaciones de la eficacia: La TRO será determinada por los investigadores basándose en RECIST versión 1.1. La TRO se define como la proporción de pacientes que habían confirmado RC o RP evaluados por el investigador utilizando RECIST versión 1.1.TRO y su IC del 95% se resumirán en la Población de Seguridad y la Población Evaluable de Eficacia
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the study
    A lo largo del estudio
    E.5.2Secondary end point(s)
    1) For Phase 1:
    • Efficacy evaluations: ORR, DOR, and DCR will be determined by investigators based on RECIST version 1.1:
    - ORR is defined as the proportion of patients who had confirmed complete response (CR) or partial response (PR) assessed by investigator using RECIST version 1.1. ORR and its 95% confidence interval (CI) will be summarized in the Safety Population and Efficacy Evaluable Population
    - DOR is defined as the time from the first determination of an objective response per RECIST version 1.1, until the first documentation of progression or death, whichever occurs first
    - DCR is defined as the proportion of patients with best overall response of CR, PR and SD. It will be summarized similarly as ORR
    • PK: Individual BGB-A333 and tislelizumab concentrations and PK parameters will be tabulated by dose cohort
    • Immunogenicity: Immunogenic responses to BGB-A333 and tislelizumab will be assessed by summarizing the number and percentage of patients by dose cohort who develop detectable antidrug antibodies

    2) For Phase 2:
    • DOR, PFS, and DCR will be determined by investigators based on RECIST version 1.1
    o PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of disease progression assessed by investigator using RECIST v1.1 or death, whichever occurs first
    • Safety and tolerability: The safety of BGB-A333 alone and in combination with tislelizumab will be assessed throughout the study by monitoring AEs and SAEs per NCI CTCAE Version 4.03, relevant physical examination, ECGs, and laboratory assessments as needed
    • PK: Individual concentrations and PK parameters of BGB-A333 and tislelizumab
    • Immunogenicity: Immunogenic responses to BGB-A333 and tislelizumab will be assessed by summarizing the number and percentage of patients who develop detectable ADAs
    1) Para la fase 1:
    • Evaluaciones de la eficacia: la TRO, DR y TCE serán determinadas por los investigadores basándose en RECIST versión 1.1:
    - La TRO se define como la proporción de pacientes que tienen una respuesta completa (RC) o respuesta parcial (RP) confirmada, evaluada por el investigador usando RECIST versión 1.1. La TRO y su intervalo de confianza (IC) del 95 % se resumirán en la población de seguridad y la población evaluable para la eficacia.
    - La DR se define como el tiempo transcurrido desde la primera determinación de una respuesta objetiva según RECIST versión 1.1 hasta la primera documentación de progresión o muerte, lo que antes suceda.
    - La TCE se define como la proporción de pacientes con mejor respuesta global de RC, RP y EE. Se resumirá de modo similar a la TRO.
    • FC: las concentraciones individuales de BGB-A333 y tislelizumab y los parámetros FC se presentarán en tablas por cohorte de dosis.
    • Inmunogenicidad: las respuestas inmunogénicas a BGB-A333 y tislelizumab se evaluarán mediante un resumen del número y porcentaje de pacientes por cohorte de dosis que desarrollan anticuerpos contra el fármaco detectables.

    2) Para la fase 2:
    • La DR, SSP y TCE serán determinadas por los investigadores basándose en RECIST versión 1.1.
    • La SSP se define como el tiempo transcurrido desde la fecha de la primera dosis de fármaco(s) del estudio hasta la fecha de la primera documentación de progresión de la enfermedad, evaluada por el investigador usando RECIST v1.1, o la muerte, lo que antes suceda.
    • Seguridad y tolerabilidad: se evaluará la seguridad de BGB-A333 en monoterapia y en combinación con tislelizumab durante todo el estudio vigilando los AA y los AAG, conforme a NCI CTCAE, versión 4.03, mediante una exploración física pertinente, ECG y evaluaciones analíticas, según sea necesario.
    • FC: concentraciones individuales y parámetros FC de BGB-A333 y tislelizumab.
    • Inmunogenicidad: las respuestas inmunogénicas a BGB-A333 y tislelizumab se evaluarán mediante un resumen del número y porcentaje de pacientes que desarrollan ACF detectables.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the study
    A lo largo del estudio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    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.8.2.4Number 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA5
    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
    Australia
    France
    New Zealand
    Spain
    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 study completion is defined as the timepoint when the final data for the study were collected after the last patient has made the final visit to the study location.
    La finalización del estudio se define como el punto de tiempo cuando los datos finales para el estudio se recopilaron después de que el último paciente haya realizado la visita final en el centro del estudio.
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    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: 152
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 16
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 37
    F.4.2.2In the whole clinical trial 168
    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)
    Standard of Care
    Estándar de cuidado
    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 Decision2018-12-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-05
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA