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   41499   clinical trials with a EudraCT protocol, of which   6826   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    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:2020-005386-13
    Sponsor's Protocol Code Number:ARC-9
    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:2021-02-01
    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 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
    Estudio de plataforma en fase Ib/II, sin enmascaramiento y aleatorizado para evaluar la seguridad y la eficacia de combinaciones terapéuticas con AB928 en pacientes con cáncer colorrectal metastásico
    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
    Estudio para evaluar la seguridad y la eficacia de combinaciones terapéuticas de AB928 en pacientes con cáncer colorrectal metastásico
    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
    B.5.3.2Town/ cityHayward
    B.5.3.3Post codeCA 94545
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 (510)-694-6200
    B.5.5Fax number+1 (510)-372-0170
    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 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 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 nameZimberelimab
    D.3.2Product code AB122
    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 INNZimberelimab
    D.3.9.2Current sponsor codeAB122
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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.3.2Product code AB680
    D.3.4Pharmaceutical form Powder for injection
    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.3.9.3Other descriptive nameA001680, A001680-A, AB680-A
    D.3.9.4EV Substance CodeSUB218819
    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 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 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
    Metastatic colorectal cancer
    Cáncer colorrectal metastásico
    E.1.1.1Medical condition in easily understood language
    Metastatic colorectal cancer
    Cáncer colorrectal metastásico
    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 etruma-based treatment combinations
    • Cohortes A (2L), B (3L) y C (>3L)
    — Eficacia: Evaluar la actividad antitumoral de las combinaciones terapéuticas con etruma
    • Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    — Seguridad: Evaluar la seguridad y la tolerabilidad de las combinaciones terapéuticas con 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
    • Cohortes A (2L), B (3L) y C (>3L)
    — Evaluar la actividad clínica de las combinaciones terapéuticas con etruma
    • Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    — Determinar el perfil farmacocinético (FC) de los componentes de las combinaciones terapéuticas con etruma
    • Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    — Evaluar la inmunogenicidad de los componentes biológicos del tratamiento combinado, cuando corresponda
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Capable of giving signed informed consent
    2.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. 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. 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. The HCV RNA test will be performed only for participants who have a positive HCV antibody test. Eligible participants must not have evidence of chronic viral hepatitis infection at screening
    13.Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

    Due to limited space, for Study Treatment-Specific Inclusion Criteria please refer to section 7.2 of the protocol
    1. Participantes capaces de proporcionar consentimiento informado(CI) firmado
    2. Hombres y mujeres mayores de edad en el momento de la firma del CI.
    3. Participantes que, en opinión del investigador, tengan capacidad para cumplir con el protocolo del estudio
    4. Participantes con adenocarcinoma colorrectal metastásico confirmado por histología
    5. Enfermedad mensurable (al menos una lesión diana) conforme a la v1.1 de los criterios de evaluación de la respuesta en tumores sólidos (RECIST). Las lesiones previamente irradiadas pueden considerarse como una enfermedad medible solo si se ha documentado inequívocamente la progresión de la enfermedad en ese lugar desde la radiación.
    Nota: El criterio de inclusión 5 no es necesario para participantes que formen parte de la cohorte de preinclusión de la seguridad
    6. Los participantes con enfermedades mensurables y tumores accesibles se someterán a una biopsia previa al tratamiento (a no ser que se disponga de una muestra de archivo) y a una biopsia tumoral nueva durante el tratamiento. La biopsia no debe suponer un riesgo indebido para los pacientes y el procedimiento no debe ser más invasivo que una biopsia con aguja gruesa, como ha documentado el investigador en la historia clínica. Se deberá hacer una biopsia nueva de una lesión del tumor que no se haya irradiado con anterioridad. Se podrán considerar aquellos tumores que hayan empeorado en un lugar de irradiación anterior tras consultarlo con el promotor.
    • Los participantes que se vayan a someter a una biopsia deben presentar al menos dos lesiones mensurables al inicio: una para obtener las muestras de tejido y otra para evaluar la respuesta radiográfica.
    7. Estado funcional del Grupo Oncológico Cooperativo del Este (ECOG) de 0 o 1.
    8. Esperanza de vida determinada por el investigador ≥3 meses
    9. Función hematológica y de órganos efectores adecuada definida mediante los siguientes resultados de las pruebas analíticas durante la selección:
    a. Recuento absoluto de neutrófilos ≥ 1,5 x 10^9/l (1500/μl) sin soporte de factores estimuladores de colonias de granulocitos. b. Recuento de leucocitos ≥ 2,5 x 10^9/l (2500/μl).c. Recuento de linfocitos ≥ 0,5 x 10^9/l (500/μl). d. Recuento de plaquetas ≥ 100 x 10^9/l (100 000/μl) sin transfusión. e. Hemoglobina ≥ 90 g/l (9,0 g/dl). Los participantes no deben haber recibido una transfusión durante las 2 semanas anteriores a la selección para cumplir los parámetros mínimos de plaquetas y hemoglobina.
    f. Aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT) ≤ 2,5 x el límite superior de la normalidad (LSN), con la siguiente excepción:
    i. Participantes con metástasis hepática documentada: AST y ALT ≤ 5 x el LSN
    ii. Participantes con metástasis hepática u ósea documentada: fosfatasa alcalina (FA) ≤ 5 x el LSN
    g. FA ≤ 5 x el LSN
    i. Si FA > 5 x el LSN, entonces la gammaglutamil transpeptidasa debe estar entre los límites normales
    h. Bilirrubina total ≤ 1,5 x el LSN, con la siguiente excepción:
    i. Participantes con síndrome de Gilbert demostrado: concentración de bilirrubina sérica ≤ 3 x el LSN
    i. Albúmina ≥ 25 g/l (2,5 g/dl)
    j. Creatinina sérica ≤ 1,5 x el LSN o aclaramiento de creatinina ≥ 30 ml/min determinado por la ecuación de Cockcroft-Gault (Cockcroft and Gault, 1976).x
    10.Resultado negativo para el virus de la inmunodeficiencia humana (VIH) durante la selección. Los participantes aptos no deben mostrar una infección crónica por VIH en la selección
    11. Test negativos para el antígeno de superficie de la hepatitis B (HBsAg) y para anticuerpos contra el antígeno central de la hepatitis B (HBcAb) o resultados positivos para el HBcAb total seguidos de un resultado negativo para el virus de la hepatitis B (VHB) durante la selección. La prueba del VHB se hará solo en participantes que hayan tenido un resultado positivo para el HBcAB total. Los participantes aptos no deben mostrar una infección crónica por hepatitis vírica en la selección
    12. Test negativo para anticuerpos del virus de la hepatitis C (VHC) durante la selección o resultado positivo para anticuerpos del VHC seguido de un resultado negativo para el ácido ribonucleico (ARN) del VHC durante la selección. La prueba de ARN del VHC se hará solo en participantes que hayan tenido un resultado positivo para anticuerpos de VHC. Los participantes aptos no deben mostrar una infección crónica por hepatitis vírica en la selección
    13. Los participantes deberán aceptar la práctica de la abstinencia sexual (abstenerse de mantener relaciones heterosexuales) o usar medidas anticonceptivas y aceptar abstenerse de donar esperma.

    Debido a las limitaciones de espacio, consulte el apartado 7.2 del protocolo relativo a los criterios de inclusión específicos del tratamiento del estudio
    E.4Principal exclusion criteria
    1.Prior anticancer treatment for the disease under study, including 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.
    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 half-lives) 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-α 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 after Medical Monitor approval.
    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 after Medical Monitor approval.
    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
    a. Participants with a history of treated CNS metastases are eligible, if all of the following criteria are met:
    i. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
    ii. Metastases are limited to the cerebellum or the supratentorial region.
    iii. There is no evidence of interim progression between completion of CNS directed therapy and the screening brain scan.
    iv. The participant has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole brain radiotherapy within 14 days prior to initiation of study treatment.
    v. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anti-convulsant therapy at a stable dose is permitted.
    b. Asymptomatic participants with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan
    10.History of leptomeningeal disease
    11.History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
    b. Participants with ground-glass opacities of unknown significance may be eligible following a discussion with the Medical Monitor. Participants must be asymptomatic and without evidence of hypoxia on ambulation.
    12.History of malignancy other than colorectal cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (eg, 5-year OS rate >90%), such as non-melanoma skin carcinoma or ductal carcinoma in situ
    13.Active tuberculosis
    14.Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
    15.Severe infection within 4 weeks (28 days) prior to initiation of study treatment,
    16.Significant cardiovascular disease within 3 months prior to initiation of study treatment

    See section 7.3 of the Protocol for a full list of Exclusion Criteria
    1. Tratamientos antineoplásicos previos para la enfermedad en estudio, incluidos aquellos en los que hayan utilizado medicamentos aprobados, radioterapia sistémica o tratamientos experimentales, durante las 4 semanas (o 5 semividas, lo que sea más corto) antes de iniciar el tratamiento del estudio. Se debe hacer una radioterapia focal al menos 2 semanas antes de iniciar el tratamiento del estudio
    2. QTc ≥ 480 ms con la fórmula de corrección de QT de Fredericia.
    3. Trasplante previo de órganos sólidos o alotrasplante de células madre.
    4. Tratamiento con inmunoestimulantes (incluidos, entre otros, el interferón y la interleucina 2) durante las 4 semanas (o 5 semividas, lo que sea más corto) antes de iniciar el tratamiento del estudio
    5. Tratamiento con inmunodepresores sistémicos (incluidos, entre otros, corticoides, ciclofosfamida, azatioprina, metotrexato, talidomida y factores de necrosis tumoral alfa) que se hayan administrado en una dosis > 10 mg/día de prednisona o una cantidad equivalente durante las 2 semanas anteriores al inicio del tratamiento del estudio, o si se ha previsto la necesidad de inmunodepresores sistémicos durante el tratamiento del estudio, con las siguientes excepciones:
    a. Los participantes que hayan recibido una dosis baja (≤ 10 mg/día de prednisona o equivalente) de inmunodepresores sistémicos o que en una sola ocasión hayan recibido una dosis pulsada de inmunodepresores sistémicos (p. ej., 48 horas de corticoides para una alergia por contacto) serán elegibles con la aprobación del supervisor médico.
    b. Los participantes que hayan recibido mineralocorticoides (p. ej., fludrocortisona), corticoides por vía intranasal o por inhalación para tratar la enfermedad pulmonar obstructiva o el asma, o una dosis baja de corticoides para tratar la hipotensión ortostática o la insuficiencia adrenal serán elegibles con la aprobación del supervisor médico.
    6. Tratamiento con una vacuna viva atenuada durante las 4 semanas previas al inicio del tratamiento del estudio o previsión de la necesidad de dicha vacuna durante el tratamiento del estudio o durante los 5 meses siguientes a la última dosis del tratamiento del estudio
    7. Tratamiento actual antivírico contra el VHB
    8. Lesiones óseas de estructura inestable que indiquen una fractura inminente
    9. Metástasis en el sistema nervioso central (SNC) sintomáticas, no tratadas o en progreso activo
    a. Los participantes con antecedentes de metástasis del SNC que se hayan tratado son aptos si se cumplen todos los criterios siguientes:
    i. El participante no tiene antecedentes de hemorragia intracraneal ni de hemorragia en la médula espinal.
    ii. Las metástasis se limitan a la región supratentorial o al cerebelo.
    iii. No hay signos de un empeoramiento temporal entre la finalización del tratamiento selectivo del SNC y el escáner cerebral de la selección.
    iv. El participante no ha recibido radioterapia estereotáctica durante los 7 días anteriores al inicio del tratamiento del estudio o radioterapia del encéfalo completo durante los 14 días anteriores al inicio del tratamiento del estudio.
    v. El paciente no necesita corticoides de manera continua para tratar alguna enfermedad del SNC. Se permite el tratamiento con anticonvulsivos en una dosis estable.
    b. Los participantes asintomáticos con metástasis del SNC que se hayan detectado recientemente durante la selección serán aptos para el estudio después de recibir radioterapia o someterse a una intervención quirúrgica, sin necesidad de repetir el escáner cerebral de la selección
    10. Antecedentes de carcinomatosis leptomeníngea
    11. Antecedentes de fibrosis pulmonar idiopática, neumonía organizada (p. ej., bronquiolitis obliterante), neumonitis farmacógena o idiopática, o signos de una neumonitis activa en la tomografía computarizada (TC) del tórax de la selección
    a. Se permite tener antecedentes de neumonitis por radiación en el campo de radiación (fibrosis)
    b. Los participantes con opacidades en vidrio esmerilado de importancia desconocida podrían ser aptos tras consultarlo con el supervisor médico. Los participantes deben ser asintomáticos y no mostrar signos de hipoxia al caminar.
    12. Antecedentes de neoplasia malignas diferentes del cáncer colorrectal durante los 2 años anteriores a la selección, excepto cuando estas presenten un riesgo insignificante de metástasis o muerte (p. ej., tasa de SG a 5 años > 90%), como por ejemplo el carcinoma cutáneo no melanómico o el carcinoma ductal in situ
    13. Tuberculosis activa
    14. Tratamiento con antibióticos terapéuticos por vía oral o intravenosa (i.v.) durante las 2 semanas anteriores al inicio del tratamiento del estudio
    15. Infecciones graves durante las 4 semanas (28 días) anteriores al inicio del tratamiento del estudio
    16. Enfermedades cardiovasculares significativas durante los 3 meses anteriores al inicio del tratamiento del estudio

    Véase el apartado 7.3 del Protocolo para la lista completa de los Criterios de exclusión.
    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)
    Eficacia:
    Cohorte A (2.ª línea [2L])
    • Supervivencia libre de progresión (SLP) conforme a la v1.1 de los criterios de evaluación de la respuesta en tumores sólidos (RECIST) evaluados por el investigador
    Cohorte B (3.ª línea [3L]) (coprincipal)
    • SLP conforme a la v1.1 de los criterios RECIST evaluados por el investigador
    • Supervivencia global (SG) Cohorte C (>3 líneas [>3L])
    • Tasa de respuesta objetiva (TRO) conforme a la v1.1 de los criterios RECIST evaluados por el investigador

    Seguridad:
    Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    • Incidencia e intensidad de los eventos adversos (EA) y los eventos adversos graves (EAG)
    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
    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
    Eficacia:
    Cohorte A (2.ª línea [2L]): SLP
    Definida como el tiempo transcurrido desde la fecha de asignación del tratamiento hasta la fecha en que se documenta por primera vez el empeoramiento de la enfermedad o la muerte, lo que ocurra primero.
    Cohorte B (3.ª línea [3L]) (coprincipal): SLP y SG
    SLP (definida antes) y SG definida como el tiempo transcurrido desde la fecha de asignación del tratamiento hasta la fecha de la muerte por cualquier causa.
    Cohorte C (>3 líneas [>3L]): TRO
    Definida como la proporción de participantes con la mejor respuesta global de RC o RP conforme a la v1.1 de los criterios RECIST

    Seguridad:
    Durante todo el ensayo
    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
    Cohorte A (2L)
    • TRO conforme a la v1.1 de los criterios RECIST evaluados por el investigador, duración de la respuesta (DR; definida como el tiempo transcurrido desde que se documenta por primera vez la respuesta de la enfermedad [respuesta completa, RC, o respuesta parcial, RP] hasta que se documenta por primera vez la progresión confirmada de la enfermedad), tasa de control de la enfermedad (TCE; definida como RC, RP o enfermedad estable [EE] durante >12 semanas) y SG
    Cohorte B (3L)
    • TRO, DR y TCE (RC, RP o EE durante >12 semanas) conforme a la v1.1 de los criterios RECIST evaluados por el investigador.
    Cohorte C (>3L)
    • DR y TCE (RC, RP o EE durante >12 semanas) conforme a la v1.1 de los criterios RECIST evaluados por el investigador
    Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    • Concentración sérica o plasmática y parámetros FC de los componentes del tratamiento combinado con etruma
    Todas las cohortes (incluida la cohorte de preinclusión de la seguridad)
    • Número y porcentaje de participantes que presentaron anticuerpos antifármaco (AAF) a los componentes biológicos del tratamiento combinado
    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
    Cohorte A (2L): TRO definida como la proporción de participantes con una mejor respuesta global de RC o RP conforme a RECIST v1.1. DR definida como el tiempo desde la primera documentación de la respuesta de la enfermedad (RC o RP) hasta la primera documentación del empeoramiento confirmado de la enfermedad. TCE definida como la proporción de participantes con una mejor respuesta global de RC, RP o EE. El tiempo necesario transcurrido para que un participante con EE se considere en control de la enfermedad es >12 semanas. SG definida como el tiempo transcurrido desde la fecha de asignación del tratamiento hasta la muerte por cualquier causa. Cohorte B (3L): TRO, DR y TCE (como definidas antes). Cohorte C (>3L): DR y TCE (como definidas antes).
    Todas las cohortes: Durante todo el ensayo
    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
    Inmunogenicidad
    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
    Estudio para evaluar la seguridad y la eficacia de combinaciones terapéuticas de AB928
    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 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) No
    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 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
    France
    Germany
    Italy
    Korea, 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
    LVLP
    Última visita último paciente
    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: 210
    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 state14
    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
    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 Decision2021-09-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-06-01
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA