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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: ABBV-453
    Oral; Tablet
Experimental
Part 2: Arm 1 		Participants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.
  • Drug: ABBV-453
    Oral; Tablet
  • Drug: Dexamethasone
    Oral Tablet
Experimental
Part 2: Arm 2 		Participants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.
  • Drug: ABBV-453
    Oral; Tablet
  • Drug: Dexamethasone
    Oral Tablet
  • Drug: Daratumumab
    Subcutaneous Injection
Experimental
Part 2: Arm 3 		Participants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.
  • Drug: ABBV-453
    Oral; Tablet
  • Drug: Dexamethasone
    Oral Tablet
  • Drug: Daratumumab
    Subcutaneous Injection
  • Drug: Lenalidomide
    Oral Capsule
Experimental
Japan Cohort 		Participants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.
  • Drug: ABBV-453
    Oral; Tablet

Recruiting Locations

Tulane University /ID# 244854
New Orleans, Louisiana 70112-2699

More Details

Status
Recruiting
Sponsor
AbbVie

Study Contact

ABBVIE CALL CENTER
844-663-3742
abbvieclinicaltrials@abbvie.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.