Relapsed or Refractory Multiple MyelomaPhase 1/2NCT07681596
A Modular, Phase I/II, Multicentre Study to Evaluate AZD4045, in Participants With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing AZD4045, Daratumumab and Aldesleukin in people with Relapsed or Refractory Multiple Myeloma, run by AstraZeneca at 12 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Multiple Myeloma
- What is being tested?
- AZD4045, Daratumumab and Aldesleukin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 27 Jul 2026to 6 Mar 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- Participant has significant neurological or psychiatric condition (active or history of).
- Participant is positive for any of the following:
- HIV (with exceptions)
- Chronic or active hepatitis B
- Active hepatitis C
- Participant has clinically significant cardiovascular disease, including but not limited to:
- Myocardial infarction within 6 months prior to eligibility confirmation, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
- Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
- Congestive heart failure Class III or IV.
- 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:
- Serious active or uncontrolled infection.
- Requirement of supplemental oxygen to maintain oxygen saturation.
- Active autoimmune disease or a history of autoimmune disease within 2 years.
- 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:
- 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.
Trial locations and contacts
12 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
12 sites in 2 countries
United States10 sites, 8 recruiting
- Not yet recruiting
Research Site
Atlanta, Georgia, 30322
- Withdrawn
Research Site
Cleveland, Ohio, 44195
- Not yet recruiting
Research Site
Denver, Colorado, 80218
- Recruiting
Research Site
Duarte, California, 91010
- Not yet recruiting
Research Site
Hackensack, New Jersey, 07601
- Recruiting
Research Site
Houston, Texas, 77030
- Withdrawn
Research Site
Milwaukee, Wisconsin, 53226
- Not yet recruiting
Research Site
Nashville, Tennessee, 37203
- Not yet recruiting
Research Site
St Louis, Missouri, 63110
- Not yet recruiting
Research Site
Tampa, Florida, 33612
Australia2 sites, 2 recruiting
- Not yet recruiting
Research Site
Camperdown, 2050
- Recruiting
Research Site
East Melbourne, 3002
About this study
Official title: 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.
Read the 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.
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Being tested
- AZD4045, Daratumumab, Aldesleukin
- Keywords
- Multiple myeloma, Relapsed or refractory multiple myeloma, RRMM, Relapsed multiple myeloma, Refractory multiple myeloma, AZD4045, CAR-T, CART, Allogeneic
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4045Biological
Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)
DaratumumabDrug
Anti-CD38 monoclonal antibody
AldesleukinDrug
Recombinant human IL-2
| Study group | Role | What they receive |
|---|---|---|
| Module 1: AZD4045 monotherapy | Experimental | Not described Receives: Biological: AZD4045 |
| Module 1: AZD4045 in association with daratumumab and aldesleukin | Experimental | Not described Receives: Biological: AZD4045; Drug: Daratumumab; Drug: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs) and serious AEs (SAEs)
Incidence and severity of adverse events (AEs) and serious AEs (SAEs)
Measured: Through study completion, an average of 2 years
Dose-limiting toxicities (DLT)
Incidence and severity of dose-limiting toxicity (DLT) events
Measured: 28 days
Secondary outcomes (11)
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
Measured: 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
Measured: 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
Measured: 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
Measured: Through study completion, an average of 2 years
Cellular kinetics - Quantification of CAR transgene levels
Determination of transgene level
Measured: Through study completion, an average of 2 years
Cellular kinetics - Tmax
Time to reach maximum AZD4045 level
Measured: Through study completion, an average of 2 years
Cellular kinetics - Cmax
Maximum AZD4045 level
Measured: Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Area under the concentration time-curve of AZD4045 level
Measured: 0 - 28 days
Cellular kinetics - Tlast
Time to last quantifiable concentration of AZD4045 level
Measured: Through study completion, an average of 2 years
Cellular kinetics - Clast
Observed concentration of AZD4045 at last quantifiable concentration
Measured: Through study completion, an average of 2 years
Cellular kinetics - AUClast
Area under the concentration time-curve of AZD4045 level
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start27 Jul 2026
- Primary completion6 Mar 2031 (estimated)
- Study completion6 Mar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07681596
- Sponsor's protocol ID
- D7540C00001
- Status last verified
- Oct 2026
- First submitted
- 26 Jun 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07681596
- Acronym / sponsor ID
- D7540C00001
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Keywords
- Multiple myeloma, Relapsed or refractory multiple myeloma, RRMM, Relapsed multiple myeloma, Refractory multiple myeloma, AZD4045, CAR-T, CART
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 101 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2026 (actual)
- Primary completion
- 6 Mar 2031 (estimated)
- Study completion
- 6 Mar 2031 (estimated)
- First posted
- 2 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Module 1: AZD4045 monotherapy | Experimental | Biological: AZD4045 |
| Module 1: AZD4045 in association with daratumumab and aldesleukin | Experimental | Biological: AZD4045, Drug: Daratumumab, Drug: Aldesleukin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- 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.
Key exclusion criteria (41 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4045Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA) | Biological | Module 1: AZD4045 in association with daratumumab and aldesleukin, Module 1: AZD4045 monotherapy |
| DaratumumabAnti-CD38 monoclonal antibody | Drug | Module 1: AZD4045 in association with daratumumab and aldesleukin |
| AldesleukinRecombinant human IL-2 | Drug | Module 1: AZD4045 in association with daratumumab and aldesleukin |
Primary outcome
Adverse events (AEs) and serious AEs (SAEs)
Time frame: Through study completion, an average of 2 years
Incidence and severity of adverse events (AEs) and serious AEs (SAEs)
Dose-limiting toxicities (DLT)
Time frame: 28 days
Incidence and severity of dose-limiting toxicity (DLT) events
11 secondary outcomes
Efficacy - Objective Response Rate (ORR)
Time frame: Through study completion, an average of 2 years
Efficacy - Complete Response Rate (CRR)
Time frame: Through study completion, an average of 2 years
Efficacy - Duration of Response (DOR)
Time frame: Through study completion, an average of 2 years
Efficacy - Time to Response (TTR)
Time frame: Through study completion, an average of 2 years
Cellular kinetics - Quantification of CAR transgene levels
Time frame: Through study completion, an average of 2 years
Cellular kinetics - Tmax
Time frame: Through study completion, an average of 2 years
Cellular kinetics - Cmax
Time frame: Through study completion, an average of 2 years
Cellular kinetics - AUC0-28d
Time frame: 0 - 28 days
Cellular kinetics - Tlast
Time frame: Through study completion, an average of 2 years
Cellular kinetics - Clast
Time frame: Through study completion, an average of 2 years
Cellular kinetics - AUClast
Time frame: Through study completion, an average of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD4045, Daratumumab and Aldesleukin in people with Relapsed or Refractory Multiple Myeloma, run by AstraZeneca at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AEs) and serious AEs (SAEs) (time frame: Through study completion, an average of 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.