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

25 de agosto de 2026 atualizado 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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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 estudo

Intervencional

Inscrição (Estimado)

101

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Austrália
      • Camperdown, Austrália, 2050
        • Ainda não está recrutando
        • Research Site
      • East Melbourne, Austrália, 3002
        • Recrutamento
        • Research Site
  • Estados Unidos
    • California
      • Duarte, California, Estados Unidos, 91010
        • Recrutamento
        • Research Site
    • Colorado
      • Denver, Colorado, Estados Unidos, 80218
        • Ainda não está recrutando
        • Research Site
    • Florida
      • Tampa, Florida, Estados Unidos, 33612
        • Ainda não está recrutando
        • Research Site
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Ainda não está recrutando
        • Research Site
    • Missouri
      • St Louis, Missouri, Estados Unidos, 63110
        • Ainda não está recrutando
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, Estados Unidos, 07601
        • Ainda não está recrutando
        • Research Site
    • Ohio
      • Cleveland, Ohio, Estados Unidos, 44195
        • Ainda não está recrutando
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37203
        • Ainda não está recrutando
        • Research Site
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Ainda não está recrutando
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, Estados Unidos, 53226
        • Ainda não está recrutando
        • Research Site

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
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)
Medicamento: Daratumumab
Anti-CD38 monoclonal antibody
Medicamento: Aldesleukin
Recombinant human IL-2

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Adverse events (AEs) and serious AEs (SAEs)
Prazo: 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)
Prazo: 28 days
Incidence and severity of dose-limiting toxicity (DLT) events
28 days

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Efficacy - Objective Response Rate (ORR)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: Through study completion, an average of 2 years
Determination of transgene level
Through study completion, an average of 2 years
Cellular kinetics - Tmax
Prazo: 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
Prazo: Through study completion, an average of 2 years
Maximum AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Prazo: 0 - 28 days
Area under the concentration time-curve of AZD4045 level
0 - 28 days
Cellular kinetics - Tlast
Prazo: 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
Prazo: 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
Prazo: 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

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

AstraZeneca

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

27 de julho de 2026

Conclusão Primária (Estimado)

6 de março de 2031

Conclusão do estudo (Estimado)

6 de março de 2031

Datas de inscrição no estudo

Enviado pela primeira vez

26 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

26 de junho de 2026

Primeira postagem (Real)

2 de julho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

27 de agosto de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

25 de agosto de 2026

Última verificação

1 de agosto de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • D7540C00001

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano 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.

Prazo de Compartilhamento de 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.

Critérios de acesso de compartilhamento 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.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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