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

NCT ID: NCT05308654

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-17
• Study Completion Date: 2025-12-31

Brief 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.

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Monotherapy Dose Escalation

Participants with relapsed or refractory (R/R) multiple myeloma (MM) will receive escalating doses of ABBV-453, until the maximum tolerated dose (MTD) is determined.

Group Type: EXPERIMENTAL

ABBV-453

Intervention Type: DRUG

Oral; Tablet

Part 2: Arm 1

Participants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.

Group Type: EXPERIMENTAL

ABBV-453

Intervention Type: DRUG

Oral; Tablet

Dexamethasone

Intervention Type: DRUG

Oral Tablet

Part 2: Arm 2

Participants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.

Group Type: EXPERIMENTAL

ABBV-453

Intervention Type: DRUG

Oral; Tablet

Dexamethasone

Intervention Type: DRUG

Oral Tablet

Daratumumab

Intervention Type: DRUG

Subcutaneous Injection

Part 2: Arm 3

Participants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.

Group Type: EXPERIMENTAL

ABBV-453

Intervention Type: DRUG

Oral; Tablet

Dexamethasone

Intervention Type: DRUG

Oral Tablet

Daratumumab

Intervention Type: DRUG

Subcutaneous Injection

Lenalidomide

Intervention Type: DRUG

Oral Capsule

Japan Cohort

Participants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.

Group Type: EXPERIMENTAL

ABBV-453

Intervention Type: DRUG

Oral; Tablet

Interventions

ABBV-453

Oral; Tablet

Intervention Type: DRUG

Dexamethasone

Oral Tablet

Intervention Type: DRUG

Daratumumab

Subcutaneous Injection

Intervention Type: DRUG

Lenalidomide

Oral Capsule

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Stanford University School of Med /ID# 242809

Stanford, California, United States

Sylvester Comprehensive Cancer Center /ID# 243417

Miami, Florida, United States

Tulane University School of Medicine /ID# 244854

New Orleans, Louisiana, United States

American Oncology Partners of Maryland /ID# 244858

Bethesda, Maryland, United States

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

Ann Arbor, Michigan, United States

Mayo Clinic - Rochester /ID# 242844

Rochester, Minnesota, United States

Memorial Sloan Kettering Cancer Center /ID# 243503

New York, New York, United States

Atrium Health Levine Cancer Institute /ID# 243420

Charlotte, North Carolina, United States

Duke Univ Med Ctr /ID# 242808

Durham, North Carolina, United States

Wake Forest Baptist Health /ID# 244252

Winston-Salem, North Carolina, United States

University of Pennsylvania /ID# 242842

Philadelphia, Pennsylvania, United States

Vanderbilt Ingram Cancer Center /ID# 242810

Nashville, Tennessee, United States

Liverpool Hospital /ID# 244826

Liverpool, New South Wales, Australia

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

Fitzroy, Victoria, Australia

St Vincent's Hospital Melbourne /ID# 244827

Fitzroy Melbourne, Victoria, Australia

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

Heidelberg, Victoria, Australia

Epworth Healthcare /ID# 248705

Richmond, Victoria, Australia

Hadassah Medical Center-Hebrew University /ID# 250484

Jerusalem, Jerusalem, Israel

The Chaim Sheba Medical Center /ID# 250482

Ramat Gan, Tel Aviv, Israel

Tel Aviv Sourasky Medical Center /ID# 250483

Tel Aviv, Tel Aviv, Israel

Barts Health NHS Trust /ID# 248972

London, London, City of, United Kingdom

Countries

United States; Australia; Israel; United Kingdom

Other Identifiers

2022-501685-22

Identifier Type: OTHER

Identifier Source: secondary_id

M21-406

Identifier Type: -

Identifier Source: org_study_id