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

AbbVie

Status and phase: Begins enrollment this month; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Lenalidomide; Drug: Etentamig; Drug: Daratumumab; Drug: Carfilzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06892522

2024-515770-27-00 (Other Identifier)

M25-059

Details and patient eligibility

About

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.

Enrollment: 440 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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440 participants in 15 patient groups

Substudy 1: Etentamig Dose Escalation

Experimental group

Description:

Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration.

Treatment:

Drug: Daratumumab

Drug: Etentamig

Drug: Lenalidomide

Substudy 1: Etentamig Dose Expansion Dose Level 1

Experimental group

Description:

Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration.

Treatment:

Drug: Daratumumab

Drug: Etentamig

Drug: Lenalidomide

Substudy 1: Etentamig Dose Expansion Dose Level 2

Experimental group

Description:

Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration.

Treatment:

Drug: Daratumumab

Drug: Etentamig

Drug: Lenalidomide

Substudy 1: Comparator

Experimental group

Description:

Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration.

Treatment:

Drug: Daratumumab

Drug: Dexamethasone

Drug: Lenalidomide

Drug: Dexamethasone

Substudy 2: Etentamig Dose Escalation

Experimental group

Description:

Participants will receive escalating etentamig, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Substudy 2: Etentamig Dose Expansion Dose Level 1

Experimental group

Description:

Participants will receive dose level 1 of etentamig, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Substudy 2: Etentamig Dose Expansion Dose Level 2

Experimental group

Description:

Participants will receive dose level 2 of etentamig, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Substudy 2: Comparator

Experimental group

Description:

Participants will receive lenalidomide (R), as part of the approximately 130 month study duration.

Treatment:

Drug: Lenalidomide

Substudy 3: Etentamig Dose Escalation

Experimental group

Description:

Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Etentamig

Drug: Dexamethasone

Substudy 3: Etentamig Dose Expansion Dose Level 1

Experimental group

Description:

Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Etentamig

Drug: Dexamethasone

Substudy 3: Etentamig Dose Expansion Dose Level 2

Experimental group

Description:

Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Etentamig

Drug: Dexamethasone

Substudy 3: Comparator

Experimental group

Description:

Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration.

Treatment:

Drug: Carfilzomib

Drug: Daratumumab

Drug: Dexamethasone

Drug: Dexamethasone

Substudy 4: Etentamig Dose Escalation

Experimental group

Description:

Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Drug: Lenalidomide

Substudy 4: Etentamig Dose Expansion Dose Level 1

Experimental group

Description:

Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Drug: Lenalidomide

Substudy 4: Etentamig Dose Expansion Dose Level 2

Experimental group

Description:

Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration.

Treatment:

Drug: Etentamig

Drug: Lenalidomide