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

NCT07681596 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: D7540C00001
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 12

Brief 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.

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; Allogeneic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Efficacy - Objective Response Rate (ORR)

  Through study completion, an average of 2 years

• Efficacy - Complete Response Rate (CRR)

  Through study completion, an average of 2 years

• Efficacy - Duration of Response (DOR)

  Through study completion, an average of 2 years

• Efficacy - Time to Response (TTR)

  Through study completion, an average of 2 years

• Cellular kinetics - Quantification of CAR transgene levels

  Through study completion, an average of 2 years

Study Arms (2)

Module 1: AZD4045 monotherapy

EXPERIMENTAL

Biological: AZD4045

Module 1: AZD4045 in association with daratumumab and aldesleukin

EXPERIMENTAL

Biological: AZD4045; Drug: Daratumumab; Drug: Aldesleukin

Interventions

AZD4045 BIOLOGICAL

Allogeneic Chimeric Antigen Receptor T cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA)

Module 1: AZD4045 in association with daratumumab and aldesleukin; Module 1: AZD4045 monotherapy

Daratumumab DRUG

Anti-CD38 monoclonal antibody

Module 1: AZD4045 in association with daratumumab and aldesleukin

Aldesleukin DRUG

Recombinant human IL-2

Module 1: AZD4045 in association with daratumumab and aldesleukin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (12)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Denver, Colorado, 80218, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Milwaukee, Wisconsin, 53226, United States

Location

Research Site

Camperdown, 2050, Australia

Location

Research Site

East Melbourne, 3002, Australia

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

daratumumab; aldesleukin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 2, 2026
• Study Start: July 9, 2026
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): October 30, 2029
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (10); AU (2)