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 surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed.
Surzetoclax 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 surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of surzetoclax 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 surzetoclax 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 surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral surzetoclax 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 surzetoclax 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.
Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
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.
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.
Sequential
ABBV-453
DrugOral Tablet
Daratumumab
DrugSubcutaneous (SC) Injection
Dexamethasone
DrugOral Tablet
Pomalidomide
DrugOral Capsule
Dose-Limiting Toxicities (DLT)s of ABBV-453
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
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.
Overall Response Rate (ORR)
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)
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)
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)
TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.
