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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Biological: AZD4045; Drug: Daratumumab; Drug: Aldesleukin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 101
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Not yet recruiting
    • Research Site
  • East Melbourne, Australia, 3002
    • Recruiting
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Not yet recruiting
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Not yet recruiting
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1: AZD4045 monotherapy	Biological: 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	Biological: AZD4045; Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA); Drug: Daratumumab; Anti-CD38 monoclonal antibody; Drug: Aldesleukin; Recombinant human IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs) and serious AEs (SAEs)	Incidence and severity of adverse events (AEs) and serious AEs (SAEs)	Through study completion, an average of 2 years
Dose-limiting toxicities (DLT)	Incidence and severity of dose-limiting toxicity (DLT) events	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Objective Response Rate (ORR)	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)	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)	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)	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	Determination of transgene level	Through study completion, an average of 2 years
Cellular kinetics - Tmax	Time to reach maximum AZD4045 level	Through study completion, an average of 2 years
Cellular kinetics - Cmax	Maximum AZD4045 level	Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d	Area under the concentration time-curve of AZD4045 level	0 - 28 days
Cellular kinetics - Tlast	Time to last quantifiable concentration of AZD4045 level	Through study completion, an average of 2 years
Cellular kinetics - Clast	Observed concentration of AZD4045 at last quantifiable concentration	Through study completion, an average of 2 years
Cellular kinetics - AUClast	Area under the concentration time-curve of AZD4045 level	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2026
• Primary Completion (Estimated): March 6, 2031
• Study Completion (Estimated): March 6, 2031

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 25, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Multiple myeloma; CAR-T; Allogeneic; RRMM; Relapsed multiple myeloma; Refractory multiple myeloma; CART; Relapsed or refractory multiple myeloma; AZD4045
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; aldesleukin; daratumumab
• Other Study ID Numbers: D7540C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 Sharing Time Frame: 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 Sharing Access Criteria

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No