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

25 agosto 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Stimato)

101

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Australia
      • Camperdown, Australia, 2050
        • Non ancora reclutamento
        • Research Site
      • East Melbourne, Australia, 3002
        • Reclutamento
        • Research Site
  • Stati Uniti
    • California
      • Duarte, California, Stati Uniti, 91010
        • Reclutamento
        • Research Site
    • Colorado
      • Denver, Colorado, Stati Uniti, 80218
        • Non ancora reclutamento
        • Research Site
    • Florida
      • Tampa, Florida, Stati Uniti, 33612
        • Non ancora reclutamento
        • Research Site
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Non ancora reclutamento
        • Research Site
    • Missouri
      • St Louis, Missouri, Stati Uniti, 63110
        • Non ancora reclutamento
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, Stati Uniti, 07601
        • Non ancora reclutamento
        • Research Site
    • Ohio
      • Cleveland, Ohio, Stati Uniti, 44195
        • Non ancora reclutamento
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37203
        • Non ancora reclutamento
        • Research Site
    • Texas
      • Houston, Texas, Stati Uniti, 77030
        • Non ancora reclutamento
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, Stati Uniti, 53226
        • Non ancora reclutamento
        • Research Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Module 1: AZD4045 monotherapy
Biologico: AZD4045
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
Sperimentale: Module 1: AZD4045 in association with daratumumab and aldesleukin
Biologico: 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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Adverse events (AEs) and serious AEs (SAEs)
Lasso di tempo: 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)
Lasso di tempo: 28 days
Incidence and severity of dose-limiting toxicity (DLT) events
28 days

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Efficacy - Objective Response Rate (ORR)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Through study completion, an average of 2 years
Determination of transgene level
Through study completion, an average of 2 years
Cellular kinetics - Tmax
Lasso di tempo: 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
Lasso di tempo: Through study completion, an average of 2 years
Maximum AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Lasso di tempo: 0 - 28 days
Area under the concentration time-curve of AZD4045 level
0 - 28 days
Cellular kinetics - Tlast
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

AstraZeneca

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

27 luglio 2026

Completamento primario (Stimato)

6 marzo 2031

Completamento dello studio (Stimato)

6 marzo 2031

Date di iscrizione allo studio

Primo inviato

26 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

26 giugno 2026

Primo Inserito (Effettivo)

2 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

27 agosto 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

25 agosto 2026

Ultimo verificato

1 agosto 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • D7540C00001

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano 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.

Periodo di condivisione 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.

Criteri di accesso alla condivisione 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.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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