Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Etentamig, ABBV-383, Cancer, Daratumumab, Lenalidomide, Dexamethasone, Carfilzomib, ABBV-2001, Iberdomide, Mezigdomide
Brief summary
Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine the safety, efficacy, and pharmacokinetics of Etentamig and ABBV-2001 in adult participants with MM. Etentamig and ABBV-2001 are investigational drugs being developed for the treatment of MM. This study is broken into 6 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants in substudies 1-4 will receive escalating doses of etentamig alone or with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R), followed by etentamig at the dose levels established during the escalation phases alone or with DR, Kd, R. Participants in substudies 1-4 can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Participants in substudies 5-6 will receive escalating doses or at the dose levels established during the escalation phases of ABBV-2001 with iberdomide or mezigdomide. Around 602 adult participants with MM will be enrolled at approximately 75 sites worldwide In substudies 1-3, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or with IV and DRd, DKd, or R. In substudie 4, participants will receive escalating doses of etentamig as Intravenous (IV) infusions followed by IV infusions of etentamig at the dose levels established during the escalation phase. In substudies 5-6, participants will receive escalating doses of ABBV-2001 as subcutaneous (SC) injections, with oral iberdomide or mezigdomide, followed by SC injections of ABBV-2001 at the dose levels established during the escalation phases with oral iberdomide or mezigdomide. The study duration is approximately 130 months. 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
Interventions
DRUGEtentamig
Intravenous (IV) Infusion
DRUGLenalidomide
Oral
DRUGDexamethasone
IV Injection
DRUGDaratumumab
Subcutaneous Injection
DRUGCarfilzomib
IV Infusion
DRUGMezigdomide
Oral
DRUGIberdomide
Oral
DRUGABBV-2001
subcutaneous (SC) Injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 of \<= 1. * Confirmed diagnosis of multiple myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria with either newly diagnosed or relapsed or refractory (RR) MM, depending on the substudy.
Exclusion criteria
* Participant who has known active central nervous system involvement of MM. * Participant who has known active infection as outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AE)s | Up to Approximately 130 Months | 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. |
| Substudy 1: Dose-Limiting Toxicity (DLT) of Etentamig + Daratumumab and Lenalidomide (DR) in Participants with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI NDMM) | Up to Approximately 8 weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
| Substudy 2: DLT of Etentamig Monotherapy as Maintenance in Participants with Transplant-Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) | Up to Approximately 8 Weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
| Substudy 3: DLT of Etentamig +Carfilzomib and Dexamethasone (Kd) Combination in Participants with Relapsed or Refractory Multiple Myeloma (RR MM) | Up to Approximately 8 Weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
| Substudy 4: DLT of Etentamig plus Lenalidomide when Given as Maintenance in Participants with TE NDMM | Up to Approximately 8 Weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
| Substudy 5: DLT of ABBV-2001 in Combination with Iberdomide in Participants with RR MM | Up to Approximately 8 Weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
| Substudy 6: DLT of ABBV-2001 in Combination with Mezigdomide in Participants with RR MM | Up to Approximately 8 Weeks | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Substudy 1, 2, 3, 4, 5, 6: Complete Response Rate | Up to Approximately 1 Year | Complete response rate is defined as complete response (CR), stringent complete response (sCR) as assessed by the international myeloma working group (IMWG) 2016 criteria for MM. |
| Substudy 1, 2, 3, 4, 5, 6: Overall Response Rate (ORR) | Up to Approximately 1 Year | The ORR is defined as the percentage of participants who achieve a best overall response of confirmed PR or better determined by IMWG criteria, prior to the initiation of subsequent myeloma therapy. |
| Substudy 1, 2, 3, 4, 5, 6: Progression Free Survival (PFS) | Up to Approximately 130 Months | PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IMWG) or death. |
| Substudy 1, 2, 3, 4, 5, 6: Duration of Response (DOR) | Up to Approximately 130 Months | DOR is defined as the time from the date of first response to the earliest occurrence of progressive disease, or death, whatever occurs first. |
| Substudy 1, 2, 3, 4, 5, 6: Time-to-Progression (TTP) | Up to Approximately 130 Months | TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression. |
| Substudy 1, 2, 3, 4, 5, 6: Minimal Residual Disease (MRD) negativity | Up to Approximately 52 Weeks | The MRD negativity rate is defined as the proportion of participants who achieve MRD negative status. |
Countries
Australia, Israel, Japan, Norway, United Kingdom, United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed