Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

A Modular, Phase I/II, Multicentre Study to Evaluate AZD4045, in Participants With Relapsed or Refractory Multiple Myeloma

25 de agosto de 2026 actualizado por: AstraZeneca

A Modular, Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, Cellular Kinetics, and Efficacy of AZD4045, an Allogeneic Chimeric Antigen Receptor-T Cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to assess the safety, tolerability, preliminary efficacy, cellular kinetics, and other exploratory endpoints of AZD4045 as a monotherapy and in association with daratumumab and aldesleukin for the treatment of adult participants with RRMM.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

This modular study aims to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of AZD4045 in participants with relapsed or refractory multiple myeloma (RRMM), and determine the recommended Phase 2 dose of AZD4045. Module 1 consists of AZD4045 as a monotherapy and in association with daratumumab and aldesleukin.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

101

Fase

  • Fase 2
  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Australia
      • Camperdown, Australia, 2050
        • Aún no reclutando
        • Research Site
      • East Melbourne, Australia, 3002
        • Reclutamiento
        • Research Site
  • Estados Unidos
    • California
      • Duarte, California, Estados Unidos, 91010
        • Reclutamiento
        • Research Site
    • Colorado
      • Denver, Colorado, Estados Unidos, 80218
        • Aún no reclutando
        • Research Site
    • Florida
      • Tampa, Florida, Estados Unidos, 33612
        • Aún no reclutando
        • Research Site
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Aún no reclutando
        • Research Site
    • Missouri
      • St Louis, Missouri, Estados Unidos, 63110
        • Aún no reclutando
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, Estados Unidos, 07601
        • Aún no reclutando
        • Research Site
    • Ohio
      • Cleveland, Ohio, Estados Unidos, 44195
        • Aún no reclutando
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37203
        • Aún no reclutando
        • Research Site
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Aún no reclutando
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, Estados Unidos, 53226
        • Aún no reclutando
        • Research Site

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

Inclusion Criteria:

  • Participant must be 18 years or older at the time of signing the informed consent form.
  • Participants must have documented diagnosis of MM according to the IMWG diagnostic criteria.

  • Participant must have one or more of the following measurable disease criteria:

    • Serum M-protein level ≥ 1.0 g/dL.
    • Urine M-protein ≥ 200 mg/24 h.
    • Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
  • ECOG performance score of 0 to 1.
  • Participant must have screening bone marrow aspirate and/or archival sample adequate for clonal sequence calibration for MRD. An archival sample obtained from any time prior is acceptable.
  • Participant must have adequate organ and bone marrow function.
  • Participant must have received at least 3 prior classes of therapy, including a PI, an IMiD, and an anti-CD38 antibody
  • Participant must have documented evidence of PD by IMWG 2016 criteria based on Investigator's determination during or after the most recent line of therapy

Exclusion Criteria:

  • Participant has a history of any grade IEC-HS and/or history of Grade ≥ 3 CRS and/or Grade ≥ 2 neurotoxicities during prior CAR-T cell therapy or T cell engaging therapy.
  • Participant has ongoing toxicity from previous anti-cancer therapy that did not resolve to baseline levels or to Grade ≤ 1 with the exception of alopecia or peripheral neuropathy.
  • Participant has a known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
  • Participant has systemic immunoglobulin light chain amyloidosis, active plasma cell leukaemia (presence of ≥ 5% of circulating plasma cells on a conventional peripheral blood smear) at time of screening, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome.
  • Participant has a history of haematologic malignancies, other than MM, regardless of remission status.
  • Participant has a history of a prior non-haematologic malignancy unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years.
  • Participant has significant neurological or psychiatric condition (active or history of).

  • Participant is positive for any of the following:

    1. HIV (with exceptions)
    2. Chronic or active hepatitis B
    3. Active hepatitis C

  • Participant has clinically significant cardiovascular disease, including but not limited to:

    1. Myocardial infarction within 6 months prior to eligibility confirmation, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
    2. Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
    3. Congestive heart failure Class III or IV.
    4. Impaired cardiac function (LVEF < 45%).

  • Participant has any other significant medical condition which, in the opinion of the Investigator, places the participant at an unacceptable risk for treatment-related complications, could interfere with the successful or safe delivery of therapy, or could interfere with evaluation of study intervention or interpretation of participant safety or study results. These include but are not limited to:

    1. Serious active or uncontrolled infection.
    2. Requirement of supplemental oxygen to maintain oxygen saturation.
    3. Active autoimmune disease or a history of autoimmune disease within 2 years.
    4. Inflammatory bowel disease requiring treatment within the past 5 years or other clinically significant gastrointestinal condition.
  • Participant received live, attenuated vaccine within 28 days prior to eligibility confirmation
  • Participant has undergone major surgery within 28 days prior to eligibility confirmation
  • Concurrent enrolment in another clinical study (unless the study is observational, or the participant is in the follow-up period of an interventional study).
  • Participant has a known life-threatening allergy, hypersensitivity, intolerance, or a contraindication to any study intervention or their excipients.
  • Participant received any prior CAR-T or CAR-NK therapy directed at any target within 6 months prior to eligibility confirmation.
  • Participant received any prior TCE therapy directed at any target within 6 months prior to eligibility confirmation.
  • Participant received any prior BCMA-targeted treatment within 6 months prior to eligibility confirmation.
  • Participant with a history of refractoriness to the most recent BCMA-targeted treatment received as defined as PD on or within 60 days of last dose or non-responsiveness (ie, did not achieve at least minimal response) on therapy.
  • Participant received prior allogeneic stem cell transplant at any time.
  • Participant received autologous stem cell transplant within 3 months prior to eligibility confirmation.
  • Participant received radiation therapy for treatment of plasmacytoma within 14 days before eligibility confirmation.

  • Participant received prior anti-tumour therapy as follows prior to the first dose of lymphodepletion:

    a) Within 7 days:

  • Immunomodulatory or cereblon E3 ligase modulatory drugs. b) Within 14 days:
  • PI therapy.
  • Monoclonal antibody treatment for MM.
  • Cytotoxic therapy.
  • Other systemic anti-myeloma therapy.
  • Radiation. c) Within 14 days or at least 5 half-lives, whichever is longer:
  • Targeted therapy, epigenetic therapy, investigational drug or used an invasive investigational medical device.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Module 1: AZD4045 monotherapy
Biológico: AZD4045
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
Experimental: Module 1: AZD4045 in association with daratumumab and aldesleukin
Biológico: AZD4045
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
Droga: Daratumumab
Anti-CD38 monoclonal antibody
Droga: Aldesleukin
Recombinant human IL-2

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Adverse events (AEs) and serious AEs (SAEs)
Periodo de tiempo: Through study completion, an average of 2 years
Incidence and severity of adverse events (AEs) and serious AEs (SAEs)
Through study completion, an average of 2 years
Dose-limiting toxicities (DLT)
Periodo de tiempo: 28 days
Incidence and severity of dose-limiting toxicity (DLT) events
28 days

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Efficacy - Objective Response Rate (ORR)
Periodo de tiempo: Through study completion, an average of 2 years
Defined as proportion of participants who achieve an overall response of PR or better according to the IMWG 2016 criteria
Through study completion, an average of 2 years
Efficacy - Complete Response Rate (CRR)
Periodo de tiempo: Through study completion, an average of 2 years
Defined as proportion of participants who achieve a CR/sCR response according to the to the IMWG 2016 criteria
Through study completion, an average of 2 years
Efficacy - Duration of Response (DOR)
Periodo de tiempo: Through study completion, an average of 2 years
Defined as the time from first documented confirmed response until date of documented PD per IMWG 2016 criteria or death due to any cause, whichever occurs first
Through study completion, an average of 2 years
Efficacy - Time to Response (TTR)
Periodo de tiempo: Through study completion, an average of 2 years
Defined as the time from infusion until the date of first documented objective response, as assessed per IMWG 2016 criteria
Through study completion, an average of 2 years
Cellular kinetics - Quantification of CAR transgene levels
Periodo de tiempo: Through study completion, an average of 2 years
Determination of transgene level
Through study completion, an average of 2 years
Cellular kinetics - Tmax
Periodo de tiempo: Through study completion, an average of 2 years
Time to reach maximum AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - Cmax
Periodo de tiempo: Through study completion, an average of 2 years
Maximum AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Periodo de tiempo: 0 - 28 days
Area under the concentration time-curve of AZD4045 level
0 - 28 days
Cellular kinetics - Tlast
Periodo de tiempo: Through study completion, an average of 2 years
Time to last quantifiable concentration of AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - Clast
Periodo de tiempo: Through study completion, an average of 2 years
Observed concentration of AZD4045 at last quantifiable concentration
Through study completion, an average of 2 years
Cellular kinetics - AUClast
Periodo de tiempo: Through study completion, an average of 2 years
Area under the concentration time-curve of AZD4045 level
Through study completion, an average of 2 years

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

AstraZeneca

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

27 de julio de 2026

Finalización primaria (Estimado)

6 de marzo de 2031

Finalización del estudio (Estimado)

6 de marzo de 2031

Fechas de registro del estudio

Enviado por primera vez

26 de junio de 2026

Primero enviado que cumplió con los criterios de control de calidad

26 de junio de 2026

Publicado por primera vez (Actual)

2 de julio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

27 de agosto de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

25 de agosto de 2026

Última verificación

1 de agosto de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • D7540C00001

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Marco de tiempo para compartir IPD

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Criterios de acceso compartido de IPD

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Suscribir