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    Summary
    EudraCT Number:2018-001456-34
    Sponsor's Protocol Code Number:CTMX-M-2029-001
    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:2018-11-05
    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 number2018-001456-34
    A.3Full title of the trial
    A Phase 1-2, First-in-Human Study of CX-2029 in Adults with
    Metastatic or Locally Advanced Unresectable Solid Tumors or
    Diffuse Large B-cell Lymphomas
    Estudio en fase I-II, primero en humanos, de CX-2029 en adultos con linfomas difusos de linfocitos B grandes o tumores sólidos no resecables localmente avanzados o metastásicos
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase 1-2, first-in-human study of CX-2029 in adults with advanced solid tumors which cannot be removed completely through surgery, or cancer of B cells, a type of white blood cell responsible for producing antibodies.
    Estudio en fase I-II, primero en humanos, de CX-2029 en adultos con cáncer de linfocitos B, un tipo de glóbulo blanco encargado de producir anticuerpos, o con tumores sólidos avanzados que no pueden extirparse totalmente mediante una intervención quirúrgica
    A.3.2Name or abbreviated title of the trial where available
    PROCLAIM-CX-2029
    A.4.1Sponsor's protocol code numberCTMX-M-2029-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03543813
    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 SponsorCytomX Therapeutics, 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 supportCytomX Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCytomX Therapeutics, Inc.
    B.5.2Functional name of contact pointAnnie Weaver
    B.5.3 Address:
    B.5.3.1Street Address151 Oyster Point Boulevard, Suite 400
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080-1913
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1650515 3185
    B.5.5Fax number+1650351 0353
    B.5.6E-mailclinicaltrials@cytomx.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 nameCX-2029
    D.3.2Product code CX-2029
    D.3.4Pharmaceutical form Powder 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 established
    D.3.9.2Current sponsor codeCX-2029
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.13.1Other medicinal product typeProbody Drug Conjugate
    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 or locally advanced unresectable solid tumor or diffuse large B-cell lymphoma
    Linfoma difuso de linfocitos B grandes o tumor sólido no resecable localmente avanzado o metastásico
    E.1.1.1Medical condition in easily understood language
    Cancer
    Cáncer
    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 HLT
    E.1.2Classification code 10012819
    E.1.2Term Diffuse large B-cell lymphomas
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10067821
    E.1.2Term Head and neck cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10033606
    E.1.2Term Pancreatic cancer non-resectable
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    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
    Part A
    The primary objective of Part A is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of CX-2029, by evaluating the overall safety profile and dose-limiting toxicities (DLTs).

    Part B
    The primary objectives of Part B are to:
    • Characterize the protease activity and measure the cleavage of CX-2029 in tumor biopsies and peripheral blood in subjects with histologically or cytologically confirmed metastatic or locally advanced HNSCC, DLBCL, NSCLC, or pancreatic cancer
    • Obtain additional characterization of the safety of CX-2029

    Part C
    The primary objective of Part C is to evaluate the antitumor activity of CX-2029 in expanded cohorts using the MTD/RP2D determined in Part A. Antitumor activity will be assessed on the basis of the ORR as determined by the RECIST v1.1 for solid tumors or the modified Lugano Classification for Lymphomas for DLBCL.
    Parte A
    El objetivo principal de la parte A es determinar la dosis máxima tolerada (DMT) o la dosis recomendada para la fase II (DRFII) de CX-2029, mediante la evaluación del perfil de seguridad global y las toxicidades limitantes de la dosis (TLD)

    Parte B
    Los objetivos principales de la parte B son:
    - Caracterizar la actividad de la proteasa y cuantificar la escisión del CX-2029 en biopsias tumorales y sangre periférica en sujetos con CECC, LDLBG, CPNM o cáncer de páncreas localmente avanzados o metastásicos, confirmados histológica o citológicamente
    - Obtener una caracterización adicional de la seguridad del CX-2029

    Parte C
    El objetivo principal de la parte C es evaluar la actividad antitumoral del CX-2029 en cohortes ampliadas utilizando la DMT/DRFII determinada en parte A. Dicha actividad se evaluará basándose en la TRO determinada según la v. 1.1 de RECIST en el caso de los tumores sólidos o la Clasificación de Lugano para los linfomas modificada en el caso del LDLBG.
    E.2.2Secondary objectives of the trial
    Part A:
    • Evaluate antitumor activity based on:
    - Objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or tumor-specific criteria, as applicable
    - Duration of response (DOR)

    • Characterize the pharmacokinetics (PK) of CX-2029 (total and intact) and MMAE (conjugated and unconjugated)
    • Assess the incidence of antidrug antibody (ADA) formation to CX-2029


    Part B:
    • Evaluate the ORR by RECIST v1.1 for solid tumors or the modified Lugano Classification for Lymphomas for DLBCL
    • Characterize the PK of CX-2029 (total and intact) and MMAE (conjugated and unconjugated)
    • Assess the incidence of ADA formation to CX-2029


    Part C:
    • Obtain additional characterization of the safety of CX-2029
    • Evaluate antitumor activity based on:
    - TTR
    - DOR
    - PFS
    - OS
    • Characterize the PK of CX-2029 (total and intact) and MMAE (conjugated and unconjugated)
    • Assess the incidence of ADA formation to CX-2029
    Parte A:
    Evaluar actividad antitumoral en función de:
    - Tasa respuesta objetiva (TRO) según v. 1.1 de criterios evaluación respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors [RECIST]) o con arreglo a criterios específicos para tumor, según proceda
    - Duración respuesta (DR)
    Caracterizar farmacocinética (FC) de CX-2029 (total/intacto) y MMAE (conjugada/conjugar)
    Evaluar incidencia formación anticuerpos antifármaco (AAF) contra CX-2029

    Parte B:
    Evaluar TRO según v. 1.1 RECIST en tumores sólidos o la Clasificación de Lugano para linfomas modificada en el caso de LDLBG
    Caracterizar la FC de CX-2029 (total/intacto) y MMAE (conjugada/sin conjugar)
    Evaluar incidencia formación AAF contra CX-2029

    Parte C:
    Obtener caracterización adicional de seguridad de CX-2029
    Evaluar actividad antitumoral en función de: TRT, DR, SSP, SG
    Caracterizar FC de CX-2029 (total/intacto) y de MMAE (conjugada/sin conjugar)
    Evaluar incidencia formación AAF contra CX-2029
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria for All Study Parts (Parts A, B, and C):
    1. At least 18 years old
    2. Ability and willingness to sign an informed consent form (ICF)
    3. Screening laboratory values must meet the following criteria:
    - Absolute neutrophil count ≥1500/μL
    - Platelet count ≥100 × 10^3/μL (no transfusion within 2 weeks)
    - Hemoglobin ≥10.0 g/dL (no transfusion within 2 weeks)
    - Creatinine ≤1.5 × institution’s upper limit of normal (ULN)
    - Both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institution’s ULN
    - Total bilirubin ≤1.5 × ULN (total bilirubin must be ≤3 × institution’s ULN in subjects with Gilbert’s syndrome)
    4. Subjects with treated brain metastases are eligible if the brain metastases are stable and the subject does not require radiation therapy or steroids. Active screening for brain metastases (eg, brain computed tomography or magnetic resonance imaging) is not required
    5. Subjects with NSCLC:
    - Must have received prior treatment with platinum-based therapy and a PD-1/PD-L1 inhibitor. A checkpoint inhibitor should have been administered if approved for the subject’s indication in their locality, alone or in combination with other therapy
    - Subjects with advanced or metastatic stage IV NSCLC with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic alterations are eligible if they have progressed on treatment or did not tolerate appropriate targeted therapy. This would include osimertinib for T790M mutation-positive NSCLC
    - Subjects with NSCLC with known ROS1 rearrangement must have received prior treatment with crizotinib
    6. Females of childbearing potential and non-sterile males must agree to practice highly effective methods of birth control for the duration of the study and for 6 months after the last dose of study drug

    Inclusion Criteria Specific for Part A, Part B, or Part C
    Part A:
    1. Histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumor
    2. Documented progression or relapse after at least 1 prior systemic therapy. Moreover, subjects must have exhausted available life prolonging therapies
    3. Measurable or evaluable per RECIST v1.1
    4. Eastern Cooperative Oncology Group (ECOG) 0 to 1
    5. Agreement to provide tumor tissue; archival, new, or recent acquisition confirmed to be available prior to initiation of study drug for performance of correlative tissue and cellular studies from a tumor site not previously irradiated

    Part B
    1. Histologically or cytologically confirmed metastatic or locally advanced unresectable HNSCC, DLBCL, NSCLC, or pancreatic cancer
    2. Subjects with HNSCC must have received a platinum-containing regimen and a PD-1 inhibitor if approved for the subject’s indication in the subject’s locality
    3. Relapsed or refractory DLBCL after 2 lines of systemic therapy. At least 1 line should contain anti-CD20-based immunochemotherapy, and subjects should not be candidates for autologous hematopoietic stem cell transplantation
    4. Subjects with pancreatic cancer should have received at least 1 line of systemic chemotherapy or chemoradiation
    5. Documented progression or relapse after at least 1 prior systemic therapy. Moreover, subjects must have exhausted available life prolonging therapies
    6. Measurable disease per RECIST v1.1 or for DLBCL must have at least one bi-dimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥1.5 cm and greatest perpendicular diameter of ≥1.0 cm at baseline. The lesion must be positive on positron emission tomography (PET) scan
    7. ECOG 0 to 1
    8. Agreement to provide archival tumor sample, if available, for performance of correlative tissue and cellular studies from a tumor site not previously irradiated
    9. Must agree to provide pretreatment and on-treatment biopsies. To be enrolled in Part B, the Investigator must consider the subject safe to biopsy and the subject must consent to biopsy collection

    Part C
    1. Histologically of cytologically confirmed metastatic or locally advanced unresectable HNSCC, DLBCL, NSCLC or pancreatic cancer
    2. Subjects with HNSCC must have received a platinum-containing regimen and a PD-1 inhibitor if approved for subject’s indication in their locality
    3. Relapsed or refractory DLBCL after 2 lines of systemic therapy. At least 1 line should contain anti-CD20 based immunochemotherapy, and subjects should not be candidates for autologous hematopoietic stem cell transplantation
    4. Subjects with pancreatic cancer should have received at least 1 line of systemic chemotherapy or chemo-radiation
    5. Documented progression or relapse after at least 1 prior systemic therapy. Moreover, subjects must have exhausted available life prolonging therapies

    Refer to study protocol for additional Part C inclusion criteria.
    Criterios incl. comunes a todas las partes del estudio (partes A, B,C):
    1. Mínimo 18 años
    2. Capacidad/disposición firmar formulario consentimiento informado (FCI)
    3. Valores análisis en selección:
    Recuento absoluto neutrófilos >= 1500/μl
    Recuento plaquetas >= 100 × 103/μl (ausencia transfusiones en 2 semanas)
    Hemoglobina >= 10,0 g/dl (ausencia transfusiones en 2 semanas)
    Creatinina <= 1,5 veces límite superior normalidad (LSN) de referencia en el centro
    AST y ALT <= 2,5 veces el LSN de ref. del centro
    Bilirrubina total <=1,5 veces el LSN (sujetos con síndrome Gilbert, bilirrubina total <= 3 veces LSN de ref. del centro)
    4. Sujetos con metástasis cerebrales tratadas podrán participar si dichas metástasis permanecen estables y no necesita radioterapia ni corticoides. No es necesario realizar pruebas sistemáticas de detección metástasis cerebrales (por ej., TAC o RNM cerebrales)
    5. Sujetos con CPNM:
    Haber recibido un tto. previo platino+inhibidor PD-1/PD-L1. Debe haberse administrado un inhibidor punto de control autorizado para la indicación del sujeto en su localidad, ya sea en monoterapia o combinado con otro tto
    Sujetos con CPNM en estadio IV avanzado o metastásico con receptor del factor de crecimiento epidérmico (EGFR) o alteraciones genómicas de la cinasa de linfoma anaplásico (ALK) pueden participar si empeorado mientras recibían tto o no toleraron tto dirigido adecuado. Entre dichos ttos. se encontraría osimertinib para CPNM con mutación T790M
    Sujetos con CPNM con reordenamiento de ROS1 conocido deben haber recibido un tto con crizotinib
    6. Mujeres en edad fértil y varones no estériles deben utilizar métodos anticonceptivos de gran eficacia durante estudio y 6 meses siguientes a última dosis fármaco del estudio

    Criterios de incl. específicos parte A, parte B o parte C
    Parte A:
    1. Tumor sólido no resecable localmente avanzado/metastásico confirmado histológica/citológicamente
    2. Progresión o recidiva documentada tras recibir, como mín, un tto sistémico previo. Además, los sujetos deben haber agotado los ttos disponibles para prolongar la vida
    3. Mensurable o evaluable según v. 1.1 RECIST
    4. ECOG entre 0 y 1
    5. Consentimiento para proporcionar tejido tumoral; disponibilidad confirmada, antes del inicio del fármaco del estudio, de tejido procedente de foco tumoral no irradiado, ya sea de archivo, nuevo u obtenido recientemente, para realización estudios de células y tejido correlativos
    Parte B
    1. CECC, LDLBG, CPNM o cáncer de páncreas no resecables localmente avanzados/metastásicos, confirmados histológica/citológicamente
    2. Sujetos con CECC deben haber recibido un tto con platino+ inhibidor PD-1 si está autorizado para la indicación del sujeto en su localidad
    3. LDLBG recidivante o refractario después de 2 líneas de tto sistémico. Una de las líneas, como mín., debe contener inmunoquimioterapia con Ac anti-CD20 y los sujetos no deben ser candidatos a un alotrasplante de progenitores hematopoyéticos
    4. Sujetos con cáncer páncreas deben haber recibido al menos 1 línea de quimioterapia o quimiorradioterapia sistémica
    5. Progresión o recidiva documentada después de recibir, como mín, un tto sistémico previo. Además, los sujetos deben haber agotado los ttos disponibles para prolongar la vida
    6. Enfermedad mensurable según v. 1.1 RECIST o, en el caso del LDLBG, el sujeto debe tener al menos un foco canceroso mensurable bidimensionalmente. La lesión debe tener un diámetro transverso mayor >=1,5 cm o un diámetro perpendicular mayor >= 1,0 cm en visita basal. La lesión debe ser detectable en una tomografía por emisión de positrones (PET)
    7. ECOG entre 0 y 1
    8. Consentimiento para proporcionar muestra tumor de archivo, si disponible, procedente de foco tumoral no irradiado para realización de estudios de células y tejido correlativos
    9. Acceder a someterse a biopsias antes y durante el tto. Para ser incluido en parte B, el investigador debe considerar que el sujeto puede ser biopsiado con seguridad y el sujeto debe acceder a realización de biopsias
    Parte C
    1. CECC, LDLBG, CPNM o cáncer de páncreas no resecables localmente avanzados/metastásicos, confirmados histológica/citológicamente
    2. Sujetos con CECC deben haber recibido un tto con platino+ inhibidor PD-1 si autorizado para la indicación del sujeto en su localidad
    3. LDLBG recidivante o refractario tras 2 líneas de tto sistémico. Una de las líneas, como mín, debe contener inmunoquimioterapia con Ac anti-CD20 y los sujetos no deben ser candidatos a un alotrasplante de progenitores hematopoyéticos
    4. Sujetos con cáncer páncreas deben haber recibido al menos 1 línea de quimioterapia o quimiorradioterapia sistémica
    5. Progresión o recidiva documentada tras recibir, como mín, un tto sistémico previo. Además, los sujetos deben haber agotado los ttos disponibles para prolongar la vida

    Consulte el protocolo del estudio para conocer otros criterios de incl. de la parte C
    E.4Principal exclusion criteria
    1. Neuropathy >Grade 1
    2. Serious concurrent illness, including, but not limited to, the following:
    - Clinically-relevant infection, including known active hepatitis B or C, human immunodeficiency virus, or non-viral infection requiring antibiotics
    - Significant cardiac disease, such as recent myocardial infarction (≤6 months prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association >Class II), uncontrolled hypertension (NCI CTCAE Version 5.0 Grade 3 or higher), uncontrolled cardiac arrhythmias, severe aortic stenosis, or ≥Grade 3 cardiac toxicity following prior chemotherapy
    - History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or clinically significant alcoholic liver disease
    - Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm
    - Psychiatric illness/social situations that would limit compliance with study requirements
    - Interstitial lung disease irrespective of etiology
    - Hepatic impairment which is moderate (Child-Pugh B) or severe (Child-Pugh C)
    - Severe renal impairment (creatinine clearance [CrCl] <30 mL/min)
    3. Concurrent systemic treatment with an anticancer biologic within 30 days prior to receiving study drug or with a non-biological anticancer drug within 14 days prior to receiving study drug
    4. History of severe allergy or anaphylactic reaction to previous monoclonal antibodies or known hypersensitivity to auristatins
    5. Unresolved acute toxicity NCI CTCAE Version 5.0 >Grade 1 (or baseline, whichever is greater) from prior anticancer therapy. Alopecia and other non-acute toxicities are acceptable
    6. History of malignancy within the previous 2 years except for localized basal cell or squamous cell skin cancers, superficial bladder cancers, or carcinoma in situ of the prostate, cervix, or breast
    7. Concurrent anticoagulation with warfarin
    8. Inability to discontinue treatment with a strong CYP3A4 inhibitor or strong CYP3A4 inducer prior to start of treatment
    9. Clinically significant iron metabolism disorders (eg, sickle cell anemia)
    10. Transfusion dependent anemia with transfusion dependency of ≥3 months
    11. Use of iron chelators
    12. Major surgery within 3 months prior to study enrollment
    13. Live vaccine within 28 days prior to planned dose
    14. Participation in an ongoing clinical study involving medications, radiation, or surgery
    15. Women who are pregnant or breast-feeding
    1. Neuropatía de grado > 1
    2. Enfermedades concomitantes graves, incluidas, entre otras, las siguientes:
    - Infección clínicamente relevante, incluida la infección activa conocida por el virus de la hepatitis B o C o el virus de la inmunodeficiencia humana, o una infección de origen no vírico para la que se precisen antibióticos
    - Enfermedad cardiaca significativa, por ejemplo, infarto de miocardio reciente (<= 6 meses antes del día 1), angina de pecho inestable, insuficiencia cardiaca congestiva sin controlar (de clase > II de acuerdo con los criterios de la New York Heart Association), hipertensión sin controlar (de grado 3 o mayor de acuerdo con la versión 5.0 de los CTCAE del Instituto Nacional del Cáncer de los EE.UU. [NCI]), arritmias cardiacas sin controlar, estenosis de la válvula aórtica grave o toxicidad cardiaca de grado >= 3 después de una quimioterapia previa.
    - Antecedentes de esclerosis múltiple u otra enfermedad desmielinizante, síndrome de Lambert-Eaton (síndrome paraneoplásico), antecedentes de ictus hemorrágico o isquémico en los 6 últimos meses, o hepatopatía alcohólica clínicamente significativa
    - Heridas o úlceras que no cicatrizan, excepto las lesiones ulcerosas causadas por la neoplasia subyacente
    - Enfermedad psiquiátrica o situaciones sociales que limitarían el cumplimiento de los requisitos del estudio
    - Enfermedad pulmonar intersticial, independientemente de la causa
    - Disfunción hepática de carácter moderado (clase B en la escala de Child-Pugh) o grave (clase C en la escala de Child-Pugh)
    - Disfunción renal grave (aclaramiento de creatinina [ClCr] < 30 ml/min)
    3. Tratamiento sistémico concomitante con un antineoplásico biológico en los 30 días previos a la administración del fármaco del estudio o con un antineoplásico no biológico en los 14 días previos a la administración del fármaco del estudio
    4. Antecedentes de alergia grave o reacción anafiláctica a anticuerpos monoclonales previos o hipersensibilidad conocida a las auristatinas
    5. Toxicidad aguda no resuelta de grado > 1 según la versión 5.0 de los CTCAE del NCI (o
    basal, lo que sea mayor) provocada por un tratamiento antineoplásico anterior. Están permitidas la alopecia y otras toxicidades no agudas
    6. Antecedentes de neoplasia maligna en los 2 años anteriores, a excepción de los carcinomas basocelulares o epidermoides localizados, neoplasias vesicales superficiales o carcinoma de próstata, cuello uterino o mama localizado
    7. Tratamiento anticoagulante simultáneo con warfarina
    8. Imposibilidad de interrumpir un tratamiento con un inhibidor potente de CYP3A4 o un inductor potente de CYP3A4 antes de empezar el tratamiento
    9. Trastorno del metabolismo del hierro clínicamente significativo (por ejemplo, anemia drepanocítica)
    10. Anemia dependiente de transfusiones, con una dependencia ≥ 3 meses
    11. Uso de quelantes del hierro
    12. Intervención de cirugía mayor en los 3 meses anteriores a la inclusión en el estudio
    13. Vacuna de microorganismos vivos en los 28 días anteriores a la administración prevista de la dosis
    14. Participación en un estudio clínico en curso con medicamentos, radiación o cirugía
    15. Mujeres embarazadas o en periodo de lactancia
    E.5 End points
    E.5.1Primary end point(s)
    Dose-limiting toxicities
    Study-drug related AEs and AEs leading to discontinuation
    Changes from baseline in clinical laboratory results and vital signs
    Toxicidades limitantes de la dosis
    AA asociados al fármaco del estudio y AA que provoquen la interrupción del fármaco
    Cambios desde la visita basal en los resultados analíticos y las constantes vitales.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
    Podrán realizarse análisis intermedios administrativos sobre seguridad y eficacia o sobre farmacocinética, inmunogenia y biomarcadores seleccionados en varios momentos antes de la finalización del estudio, con objeto de facilitar decisiones sobre el programa y respaldar presentaciones o publicaciones sobre el estudio.
    E.5.2Secondary end point(s)
    Objective Response Rate (ORR) is the primary efficacy endpoint.
    Duration of response (DOR).
    Time To Tumor Response (TTR).
    Progression-free survival (PFS).
    Overall survival (OS).
    La tasa de respuesta objetiva (TRO) es el criterio principal de valoración de la eficacia.
    Duración de la respuesta (DR).
    Tiempo hasta la respuesta tumoral (TRT).
    Supervivencia sin progresión (SSP).
    Supervivencia global (SG).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Administrative interim analyses on safety and efficacy or on PK,
    immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
    Podrán realizarse análisis intermedios administrativos sobre seguridad y eficacia o sobre farmacocinética, inmunogenia y biomarcadores seleccionados en varios momentos antes de la finalización del estudio, con objeto de facilitar decisiones sobre el programa y respaldar presentaciones o publicaciones sobre el 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 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 Yes
    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
    Inmunogenia.
    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 trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    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
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    UVUS (Última visita del último sujeto)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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: 130
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 72
    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 state17
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 202
    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 study completion, subjects who continue to receive clinical benefit (as judged by the Investigator) may rollover to a companion protocol, if available.
    Tras finalizar el estudio, los sujetos que sigan obteniendo beneficio clínico (a juicio del investigador) podrán cambiar a un protocolo suplementario, si lo hubiera.
    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 Decision2019-01-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-20
    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
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