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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05308654
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	AbbVie
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	ABBVIE INC.
Principal Investigator Affiliation	AbbVie
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Israel, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Relapsed/Refractory Multiple Myeloma

Arms & Interventions

Arms

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.

Experimental: Part 2: Arm 1

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

Experimental: Part 2: Arm 2

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

Experimental: Part 2: Arm 3

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

Experimental: Japan Cohort

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

Interventions

Drug: - ABBV-453

Oral; Tablet

Drug: - Dexamethasone

Oral Tablet

Drug: - Daratumumab

Subcutaneous Injection

Drug: - Lenalidomide

Oral Capsule

Contact a Trial Team

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Stanford, California

Status

Recruiting

Address

Stanford University School of Med /ID# 242809

Stanford, California, 94305-2200

Site Contact

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