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Relapsed/Refractory Multiple MyelomaPhase 1NCT05308654

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets

A Phase 1 study testing ABBV-453, Dexamethasone and Daratumumab in people with Relapsed/Refractory Multiple Myeloma, run by AbbVie at 21 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of ABBV-453 in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed/Refractory Multiple Myeloma
What is being tested?
ABBV-453, Dexamethasone and Daratumumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
21 sitesin 4 countries
Study dates
17 May 2022to Dec 2025
Phase
Phase 1
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

  • Eastern Cooperative Oncology Group (ECOG) performance status <= 1.
  • Laboratory values meeting the criteria outlined in the protocol.
  • Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria.
  • Has measurable disease at screening as defined in the protocol.
  • Locally documented or centrally determined t(11;14) positive status and/or centrally determined BCL2high status. Note: If local testing for t(11;14) is discordant with central testing for t(11;14) status, a detailed review of central and local results for t(11;14) status is required to ensure the participants' safety.
  • Part 1 and Part 2, Arm 1 Only: Refractory to or intolerant of all established MM therapies that are known to provide clinical benefit and are triple class exposed to a proteasome inhibitors (PI), an Immunomodulatory drugs (IMID), and an anti-CD38 monoclonal antibody in previous line(s) of therapy.
Show all 9Show fewer
  • Part 2, Arms 2 and 3 Only: Received 1 to 3 prior lines of therapy, including a PI or an IMiD.
  • Part 1 only: Permitted to be venetoclax or BCL-2 inhibitor exposed in previous lines of therapy.
  • Life expectancy >= 12 weeks.

Who cannot join

  • Clinically relevant or significant Electrocardiogram (ECG) abnormalities as outlined in the protocol.
  • Part 2 only: Previous treatment with venetoclax or BCL-2 inhibitor.
  • Part 2, Arms 2 and 3 only: Prior daratumumab or other anti-CD38 therapy exposure that meets any of the criteria outlined in the protocol.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

United States12 sites

  • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 242754

    Ann Arbor, Michigan, 48109

  • American Oncology Partners of Maryland /ID# 244858

    Bethesda, Maryland, 20817

  • Atrium Health Levine Cancer Institute /ID# 243420

    Charlotte, North Carolina, 28204-2990

  • Duke Univ Med Ctr /ID# 242808

    Durham, North Carolina, 27710

  • Sylvester Comprehensive Cancer Center /ID# 243417

    Miami, Florida, 33136-1002

  • Vanderbilt Ingram Cancer Center /ID# 242810

    Nashville, Tennessee, 37232-0021

  • Tulane University School of Medicine /ID# 244854

    New Orleans, Louisiana, 70112

  • Memorial Sloan Kettering Cancer Center /ID# 243503

    New York, New York, 10065-6007

  • University of Pennsylvania /ID# 242842

    Philadelphia, Pennsylvania, 19104-5502

  • Mayo Clinic - Rochester /ID# 242844

    Rochester, Minnesota, 55905-0001

  • Stanford University School of Med /ID# 242809

    Stanford, California, 94305-2200

  • Wake Forest Baptist Health /ID# 244252

    Winston-Salem, North Carolina, 27157-0001

Other trials in United States

Australia5 sites

  • St. Vincent's Private Hospital Melbourne /ID# 262631

    Fitzroy, Victoria, 3065

  • St Vincent's Hospital Melbourne /ID# 244827

    Fitzroy Melbourne, Victoria, 3065

  • Austin Health and Ludwig Institute for Cancer Research /ID# 248311

    Heidelberg, Victoria, 3084

  • Liverpool Hospital /ID# 244826

    Liverpool, New South Wales, 2170

  • Epworth Healthcare /ID# 248705

    Richmond, Victoria, 3121

Other trials in Australia

Israel3 sites

  • Hadassah Medical Center-Hebrew University /ID# 250484

    Jerusalem, Jerusalem, 91120

  • The Chaim Sheba Medical Center /ID# 250482

    Ramat Gan, Tel Aviv, 5265601

  • Tel Aviv Sourasky Medical Center /ID# 250483

    Tel Aviv, Tel Aviv, 6423906

Other trials in Israel

United Kingdom1 site

  • Barts Health NHS Trust /ID# 248972

    London, London, City of, E1 2ES

Other trials in United Kingdom

About this study

Official title: First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects With Relapsed or Refractory Multiple Myeloma

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of ABBV-453 in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed.

ABBV-453 is an investigational drug being developed for the treatment of R/R MM. Part 1 will be a monotherapy dose escalation phase to determine the best dose of ABBV-453. In Part 2, participants are placed in 1 of 3 groups called treatment arms. Each group receives a different treatment. Approximately 28 to 48 adult participants in Part 1 and 150 to 312 adult participants in Part 2 with R/R MM will be enrolled in the study in approximately 70 sites worldwide.

Read more

In Part 1 and the Japan Cohort, Participants will receive oral ABBV-453 tablets once daily (QD) in 28-day cycles. In Part 2, Arm 1, participants will receive continuous doses of oral ABBV-453 tablets QD in combination with oral dexamethasone tablets once weekly in 28-day cycles. In Part 2, Arm 2, participants will receive continuous doses of oral ABBV-453 tablets QD in combination with subcutaneous injections of daratumumab every 1 to 4 weeks and oral dexamethasone tablets once weekly in, 28-day cycles. In Part 2, Arm 3, participants will receive continuous doses of oral ABBV-453 tablets QD in combination with subcutaneous injections of daratumumab every 1 to 4 weeks, oral lenalidomide capsules QD on Days 1-21, and oral dexamethasone tablets once weekly, in 28-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Being tested
ABBV-453, Dexamethasone, Daratumumab, Lenalidomide
Keywords
Relapsed/Refractory Multiple Myeloma, ABBV-453, Cancer
Medical subject headings
Multiple Myeloma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05308654
Study groupRoleWhat they receive
Part 1: Monotherapy Dose EscalationExperimentalParticipants with relapsed or refractory (R/R) multiple myeloma (MM) will receive escalating doses of ABBV-453, until the maximum tolerated dose (MTD) is determined.
Receives: Drug: ABBV-453
Part 2: Arm 1ExperimentalParticipants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.
Receives: Drug: ABBV-453; Drug: Dexamethasone
Part 2: Arm 2ExperimentalParticipants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.
Receives: Drug: ABBV-453; Drug: Dexamethasone; Drug: Daratumumab
Part 2: Arm 3ExperimentalParticipants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.
Receives: Drug: ABBV-453; Drug: Dexamethasone; Drug: Daratumumab; Drug: Lenalidomide
Japan CohortExperimentalParticipants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.
Receives: Drug: ABBV-453

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria

    ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of partial response (PR) + very good partial response (VGPR) + complete response (CR) + stringent complete response (sCR) as assessed by investigators per adapted IMWG criteria for relapsed or refractory (R/R) multiple myeloma (MM).

    Measured: Up to Approximately 12 Months

Secondary outcomes (4)

  1. Duration of Response (DOR)

    DOR is defined for participants achieving a confirmed sCR/CR/VGPR/PR as the time from the initial response of sCR/CR/VGPR/PR per investigator review according to adapted IMWG criteria to disease progression or death of any cause, whichever occurs earlier.

    Measured: Up to Approximately 24 Months

  2. Depth of Response Minimal Residual Disease (MRD)

    MRD negativity is defined as having less than 1 myeloma cell that may remain in the bone marrow aspirate. Depth of response is defined as the proportion of MRD negativity for participants achieving a confirmed sCR/CR per investigator review according to IMWG criteria.

    Measured: Up to Approximately 24 Months

  3. Progression Free Survival (PFS)

    PFS is defined as time from first study treatment to a documented disease progression according to adapted IMWG criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.

    Measured: Up to Approximately 36 Months

  4. Overall Survival (OS)

    Overall survival (OS) is defined as time from first study treatment to death due to any cause.

    Measured: Up to Approximately 36 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2022
  2. Study start17 May 2022
  3. Primary completion7 Feb 2024
  4. Study completionDec 2025 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05308654
Sponsor's protocol ID
M21-406
Other IDs
2022-501685-22
Status last verified
Aug 2025
First submitted
25 Mar 2022
Last updated
14 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABBV-453, Dexamethasone and Daratumumab in people with Relapsed/Refractory Multiple Myeloma, run by AbbVie at 21 sites in 4 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 9 inclusion and 3 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: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia, Israel, United Kingdom. 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 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.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria (time frame: Up to Approximately 12 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05308654.

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 14 Aug 2025.

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