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NCT Number: NCT05308654

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

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.

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Relapsed/Refractory Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Liverpool Hospital /ID# 244826, Liverpool, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

ABBV-453

Drug

Oral; Tablet

Dexamethasone

Drug

Oral Tablet

Daratumumab

Drug

Subcutaneous Injection

Lenalidomide

Drug

Oral Capsule

Primary outcomes

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

    Time frame: Up to Approximately 12 Months

    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).

Secondary outcomes

  1. Duration of Response (DOR)

    Time frame: Up to Approximately 24 Months

    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.

  2. Depth of Response Minimal Residual Disease (MRD)

    Time frame: Up to Approximately 24 Months

    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.

  3. Progression Free Survival (PFS)

    Time frame: Up to Approximately 36 Months

    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.

  4. Overall Survival (OS)

    Time frame: Up to Approximately 36 Months

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

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Apr 4, 2022
Registry last updated
Aug 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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