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

NCT05308654 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: M21-4062022-501685-22
• Study Type: interventional
• Target: 34
• Locations: 4 countries
• Sites: 21

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

Keywords

Relapsed/Refractory Multiple Myeloma; ABBV-453; Cancer

Outcome Measures

Primary Outcomes (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).

  Up to Approximately 12 Months

Secondary Outcomes (4)

• Duration of Response (DOR)

  Up to Approximately 24 Months

• Depth of Response Minimal Residual Disease (MRD)

  Up to Approximately 24 Months

• Progression Free Survival (PFS)

  Up to Approximately 36 Months

• Overall Survival (OS)

  Up to Approximately 36 Months

Study Arms (5)

Part 1: Monotherapy Dose Escalation

EXPERIMENTAL

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.

Drug: ABBV-453

Part 2: Arm 1

EXPERIMENTAL

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

Drug: ABBV-453; Drug: Dexamethasone

Part 2: Arm 2

EXPERIMENTAL

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

Drug: ABBV-453; Drug: Dexamethasone; Drug: Daratumumab

Part 2: Arm 3

EXPERIMENTAL

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

Drug: ABBV-453; Drug: Dexamethasone; Drug: Daratumumab; Drug: Lenalidomide

Japan Cohort

EXPERIMENTAL

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

Drug: ABBV-453

Interventions

ABBV-453 DRUG

Oral; Tablet

Japan Cohort; Part 1: Monotherapy Dose Escalation; Part 2: Arm 1; Part 2: Arm 2; Part 2: Arm 3

Dexamethasone DRUG

Oral Tablet

Part 2: Arm 1; Part 2: Arm 2; Part 2: Arm 3

Daratumumab DRUG

Subcutaneous Injection

Part 2: Arm 2; Part 2: Arm 3

Lenalidomide DRUG

Oral Capsule

Part 2: Arm 3

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (21)

Stanford University School of Med /ID# 242809

Stanford, California, 94305-2200, United States

Location

Sylvester Comprehensive Cancer Center /ID# 243417

Miami, Florida, 33136-1002, United States

Location

Tulane University School of Medicine /ID# 244854

New Orleans, Louisiana, 70112, United States

Location

American Oncology Partners of Maryland /ID# 244858

Bethesda, Maryland, 20817, United States

Location

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

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic - Rochester /ID# 242844

Rochester, Minnesota, 55905-0001, United States

Location

Memorial Sloan Kettering Cancer Center /ID# 243503

New York, New York, 10065-6007, United States

Location

Atrium Health Levine Cancer Institute /ID# 243420

Charlotte, North Carolina, 28204-2990, United States

Location

Duke Univ Med Ctr /ID# 242808

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Health /ID# 244252

Winston-Salem, North Carolina, 27157-0001, United States

Location

University of Pennsylvania /ID# 242842

Philadelphia, Pennsylvania, 19104-5502, United States

Location

Vanderbilt Ingram Cancer Center /ID# 242810

Nashville, Tennessee, 37232-0021, United States

Location

Liverpool Hospital /ID# 244826

Liverpool, New South Wales, 2170, Australia

Location

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

Fitzroy, Victoria, 3065, Australia

Location

St Vincent's Hospital Melbourne /ID# 244827

Fitzroy Melbourne, Victoria, 3065, Australia

Location

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

Heidelberg, Victoria, 3084, Australia

Location

Epworth Healthcare /ID# 248705

Richmond, Victoria, 3121, Australia

Location

Hadassah Medical Center-Hebrew University /ID# 250484

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 250482

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 250483

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Barts Health NHS Trust /ID# 248972

London, London, City of, E1 2ES, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

Dexamethasone; daratumumab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: April 4, 2022
• Study Start: May 17, 2022
• Primary Completion: February 7, 2024
• Study Completion: December 1, 2025
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); AU (5); IL (3); GB (1)