A Study to Assess Adverse Events and Change in Disease Activity of Oral ABBV-453 Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT06953960
- Lead Sponsor
- AbbVie
- 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 change in disease activity 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. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of ABBV-453 alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 sites worldwide.
In Substudy 1 escalation phase, participants will receive oral ABBV-453 tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral ABBV-453 tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral ABBV-453 tablets. The total study duration is approximately 4.5 years.
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. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 130
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Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
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All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:
- Serum M-protein >= 0.5 g/dL (>= 5g/L); OR
- Urine M-protein >= 200 mg/24 hours; OR
- For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) ≥ 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
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B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
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t(11;14) positive status and/or BCL2 high status.
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Substudy 1 Dose Escalation Cohorts and Substudy 2:
-- Must be triple class exposed (PI, IMiD and anti-CD38) and have received 3 to 5 lines of prior antimyeloma therapy, and who have no other appropriate treatment options as deemed by the investigator.
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Substudy 1 Dose Expansion Cohorts:
- Must be double class exposed (PI, IMiD) and have received 1 to 3 lines of prior antimyeloma therapy.
- Major surgery within 4 weeks of study treatment or planned during study participation.
- Active infections: no recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled systemic infection.
- Recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled active systemic infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Substudy 1: Dose Escalation ABBV-453 Combination ABBV-453 Participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration. Substudy 1: Dose Escalation ABBV-453 Combination Daratumumab Participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration. Substudy 1: Dose Escalation ABBV-453 Combination Dexamethasone Participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection ABBV-453 Combination ABBV-453 Participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection ABBV-453 Combination Daratumumab Participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection ABBV-453 Combination Dexamethasone Participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection Control Daratumumab Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection Control Dexamethasone Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration. Substudy 1: Dose Expansion and Selection Control Pomalidomide Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration. Substudy 2: Dose Escalation ABBV-453 Monotherapy ABBV-453 Japanese participants will receive various doses of ABBV-453 as a monotherapy, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration.
- Primary Outcome Measures
Name Time Method Dose-Limiting Toxicities (DLT)s of ABBV-453 Up to Approximately 45 Months DLT events are defined as specific clinically significant adverse events or abnormal laboratory values assessed as events regardless of attribution to ABBV-453, except those clearly and incontrovertibly associated with underlying disease or extraneous causes.
Number of Participants with Adverse Events (AE)s Up to Approximately 4.5 Years An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
- Secondary Outcome Measures
Name Time Method Minimal Residual Disease (MRD) Negativity Up to Approximately 4.5 Years MRD negativity is defined as having less than 1 myeloma cell that may remain in the bone marrow aspirate per 10\^5 nucleated cells and rate of MRD negativity will be determined.
Overall Survival (OS) Up to Approximately 4.5 Years OS is defined as time from first study treatment to death due to any cause.
Overall Response Rate (ORR) Up to Approximately 4.5 Years ORR is defined as the percentage of participants with a confirmed partial response (PR), very good partial response, complete response (CR) or stringent complete response (sCR) per Investigator review according to International Myeloma Working Group (IMWG) 2016 criteria.
Progression-Free Survival (PFS) Up to Approximately 4.5 Years PFS is defined as time from first study treatment to the earliest documented disease progression according to IMWG 2016 criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.
Duration of Response (DOR) Up to Approximately 4.5 Years DOR is defined as the time from the date of achieving the first confirmed sCR/CR/VGPR/PR to the date of recurrence disease progression according to IMWG 2016 criteria, as determined by the investigator, or death of any cause, whichever occurs earlier.
Time-to-Progression (TTP) Up to Approximately 4.5 Years TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.
Time to Next Treatment Up to Approximately 4.5 Years Time to next treatment will be defined as the number of days from the date of first dose to the date of next treatment.