Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Relapsed/Refractory Multiple Myeloma, ABBV-453, Cancer
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.
Interventions
DRUGABBV-453
Oral; Tablet
DRUGDexamethasone
Oral Tablet
DRUGDaratumumab
Subcutaneous Injection
DRUGLenalidomide
Oral Capsule
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria | 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | 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. |
| Depth of Response Minimal Residual Disease (MRD) | 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. |
| Progression Free Survival (PFS) | 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. |
| Overall Survival (OS) | Up to Approximately 36 Months | Overall survival (OS) is defined as time from first study treatment to death due to any cause. |
Countries
Australia, Israel, United Kingdom, United States
Outcome results
None listed