Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, ABBV-453, Surzetoclax, Daratumumab, Dexamethasone, Pomalidomide, 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 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 dose escalation and dose expansion phases where participants will receive various doses (escalation) or 1 of 2 doses (expansion) of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. In Substudy 3 there will be dose escalation and optimization phases where participants will receive various doses (escalation) or 1 of 2 doses (optimization) of of surzetoclax and etentamig to determine the best dose of surzetoclax and etentamig. Optimization will also include etentamig received alone. Approximately 325 adult participants with R/R MM will be enrolled in the study in approximately 55 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 1 of 2 doses 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. In Substudy 3 escalation phase, participants will receive oral surzetoclax tablets in combination with IV etentamig and in the expansion phase, will receive 1 of 2 doses of both oral surzetoclax tablets in combination with of IV etentamig, or IV etentamig alone. 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.
Interventions
DRUGSurzetoclax
Oral
DRUGDaratumumab
Subcutaneous (SC) Injection
DRUGDexamethasone
Oral
DRUGPomalidomide
Oral
DRUGEtentamig
Intravenous Infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria. * 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. * B-cell lymphoma (BCL)-2 inhibitor treatment naïve. * t(11;14) positive status and/or BCL2 high status. * Must have confirmed diagnosis of relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen, based on the investigator's determination of the international myeloma working group (IMWG) 2016 criteria.
Exclusion criteria
* Major surgery within 4 weeks of study treatment or planned during study participation. * Recent infection requiring systemic treatment that was completed \<= 14 days before first dose of study treatment and/or uncontrolled active systemic infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 (VGPR), 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. |
| 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. 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. |
Countries
Australia, Belgium, France, Germany, Israel, Italy, Japan, Poland, Portugal, Sweden, United Kingdom, United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed