A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving Etentamig (ABBV-383) as an Intravenous (IV) Infusion Alone or in Combination With Oral, IV, Subcutaneous Daratumumab; Lenalidomide; Dexamethasone; Carfilzomib
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT06892522
- Lead Sponsor
- AbbVie
- 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 in adult participants with MM.
Etentamig is an investigational drug being developed for the treatment of MM. This study is broken into 4 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants will receive escalating doses of etentamig alone or in combination with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R). This will be followed by etentamig at the dose levels established during the escalation phases alone or in combination with DR, Kd, R. The participants can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Around 440 adult participants with MM will be enrolled at approximately 50 sites worldwide
In all substudies, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or in combination with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or in combination with IV and oral DRd, DKd, or R. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 440
- 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.
- Participant who has known active central nervous system involvement of MM.
- Participant who has known active infection as outlined in the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1: Etentamig Dose Escalation Etentamig Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Escalation Lenalidomide Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Escalation Daratumumab Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 1 Etentamig Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 1 Lenalidomide Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 1 Daratumumab Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 2 Etentamig Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 2 Lenalidomide Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Etentamig Dose Expansion Dose Level 2 Daratumumab Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration. Substudy 1: Comparator Lenalidomide Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration. Substudy 1: Comparator Dexamethasone Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration. Substudy 1: Comparator Daratumumab Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration. Substudy 2: Etentamig Dose Escalation Etentamig Participants will receive escalating etentamig, as part of the approximately 130 month study duration. Substudy 2: Etentamig Dose Expansion Dose Level 1 Etentamig Participants will receive dose level 1 of etentamig, as part of the approximately 130 month study duration. Substudy 2: Etentamig Dose Expansion Dose Level 2 Etentamig Participants will receive dose level 2 of etentamig, as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 2 Etentamig Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 2 Dexamethasone Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 2 Carfilzomib Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 2: Comparator Lenalidomide Participants will receive lenalidomide (R), as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 1 Etentamig Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Escalation Etentamig Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Escalation Dexamethasone Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Escalation Carfilzomib Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 1 Dexamethasone Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 3: Etentamig Dose Expansion Dose Level 1 Carfilzomib Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration. Substudy 3: Comparator Dexamethasone Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration. Substudy 3: Comparator Daratumumab Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration. Substudy 3: Comparator Carfilzomib Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Escalation Etentamig Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Escalation Lenalidomide Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Expansion Dose Level 1 Etentamig Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Expansion Dose Level 1 Lenalidomide Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Expansion Dose Level 2 Etentamig Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration. Substudy 4: Etentamig Dose Expansion Dose Level 2 Lenalidomide Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Substudy 1, 2, 3, 4: 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: 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: 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: 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: 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.
Substudy 1, 2, 3, 4: 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.
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Trial Locations
- Locations (8)
Icon Cancer Care - South Brisbane /ID# 271836
🇦🇺South Brisbane, Queensland, Australia
Colorado Blood Cancer Institute /ID# 273129
🇺🇸Denver, Colorado, United States
The Perth Blood Institute - West Perth /ID# 272469
🇦🇺West Perth, Western Australia, Australia
The Chaim Sheba Medical Center /ID# 271366
🇮🇱Ramat Gan, Tel-Aviv, Israel
Rambam Health Care Campus /ID# 271364
🇮🇱Haifa, Israel
Hadassah Medical Center-Hebrew University /ID# 271362
🇮🇱Jerusalem, Israel
Rabin Medical Center /ID# 271365
🇮🇱Petah Tikva, Israel
The University of Osaka Hospital /ID# 275791
🇯🇵Suita-shi, Osaka, Japan
Icon Cancer Care - South Brisbane /ID# 271836🇦🇺South Brisbane, Queensland, Australia