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

25 augustus 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

101

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • Australië
      • Camperdown, Australië, 2050
        • Nog niet aan het werven
        • Research Site
      • East Melbourne, Australië, 3002
        • Werving
        • Research Site
  • Verenigde Staten
    • California
      • Duarte, California, Verenigde Staten, 91010
        • Werving
        • Research Site
    • Colorado
      • Denver, Colorado, Verenigde Staten, 80218
        • Nog niet aan het werven
        • Research Site
    • Florida
      • Tampa, Florida, Verenigde Staten, 33612
        • Nog niet aan het werven
        • Research Site
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30322
        • Nog niet aan het werven
        • Research Site
    • Missouri
      • St Louis, Missouri, Verenigde Staten, 63110
        • Nog niet aan het werven
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, Verenigde Staten, 07601
        • Nog niet aan het werven
        • Research Site
    • Ohio
      • Cleveland, Ohio, Verenigde Staten, 44195
        • Nog niet aan het werven
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Verenigde Staten, 37203
        • Nog niet aan het werven
        • Research Site
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • Nog niet aan het werven
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, Verenigde Staten, 53226
        • Nog niet aan het werven
        • Research Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Module 1: AZD4045 monotherapy
Biologisch: AZD4045
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
Experimenteel: Module 1: AZD4045 in association with daratumumab and aldesleukin
Biologisch: AZD4045
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
Geneesmiddel: Daratumumab
Anti-CD38 monoclonal antibody
Geneesmiddel: Aldesleukin
Recombinant human IL-2

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Adverse events (AEs) and serious AEs (SAEs)
Tijdsspanne: 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)
Tijdsspanne: 28 days
Incidence and severity of dose-limiting toxicity (DLT) events
28 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Efficacy - Objective Response Rate (ORR)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: Through study completion, an average of 2 years
Determination of transgene level
Through study completion, an average of 2 years
Cellular kinetics - Tmax
Tijdsspanne: 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
Tijdsspanne: Through study completion, an average of 2 years
Maximum AZD4045 level
Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Tijdsspanne: 0 - 28 days
Area under the concentration time-curve of AZD4045 level
0 - 28 days
Cellular kinetics - Tlast
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

AstraZeneca

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

27 juli 2026

Primaire voltooiing (Geschat)

6 maart 2031

Studie voltooiing (Geschat)

6 maart 2031

Studieregistratiedata

Eerst ingediend

26 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

26 juni 2026

Eerst geplaatst (Werkelijk)

2 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

27 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

25 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • D7540C00001

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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.

IPD-tijdsbestek voor delen

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.

IPD-toegangscriteria voor delen

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.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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