A Study to Assess A Change in Disease Activity and Adverse Events of Intravenous Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Adult Participants With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

AbbVie

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Multiple Myeloma

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

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT07095452

M25-586

2025-520897-21 (Other Identifier)

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. This is a study to determine the adverse events, change in disease activity, 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 2 phases; phase 2 with 3 study arms and phase 3 with 2 study arms. Participants in phase 2 will receive 1 of 3 doses of etentamig in combination with daratumumab. Participants in phase 3 will receive etentamig at RP3D in combination with daratumumab, or daratumumab, lenalidomide, and dexamethasone (DRd). Around 660 adult participants with MM will be enrolled at approximately 155 sites worldwide

Participants in phase 2 will receive 1 of 3 doses of etentamig as intravenous (IV) infusions, combination with subcutaneous (SC) injections of daratumumab. Participants in phase 3 will receive RP3D doses of etentamig as IV infusions, combination with SC injections of daratumumab, or SC injections of daratumumab, capsules of lenalidomide, and tablet/ IV injections of dexamethasone (DRd). The study duration is approximately 16 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Enrollment: 660 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have confirmed new diagnosis of multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) diagnostic criteria, and per investigator's judgement, participant is not suitable to receive high-dose chemotherapy and stem cell transplantation due to factors likely to have a negative impact on tolerability of high dose chemotherapy and autologous stem cell transplants (ASCT).

• IMWG Myeloma Frailty Index Score of >= 1

• 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 (>= 5 g/L).
  • Urine M-protein >= 200 mg/24 hours.
  • Serum free light chain (FLC) >= 100 mg/L (>= 10 mg/dL) (involved light chain) and an abnormal serum kappa lambda ratio only for participants without measurable serum or urine M-protein.

Exclusion criteria

• Prior or current systemic therapy or stem cell transplant (SCT) for multiple myeloma or any plasma cell dyscrasia other than short course of corticosteroids
• Participant treated with any investigational treatment within 30 days or 5 half-lives of the treatment (whichever is longer) prior to the first dose of study treatment or is currently enrolled in another clinical study
• Participant who has known active central nervous system involvement of MM.
• Participant who has history of clinically significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, pulmonary, or hepatic disease within the last 6 months that, in the investigator's opinion, would adversely affect the participant's participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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660 participants in 5 patient groups

Phase 2: Etentamig + Daratumumab Dose A

Experimental group

Description:

Participants will receive etentamig dose A in combination with daratumumab until the recommended phase 3 dose (RP3D), as part of the approximately 16 year study duration.

Treatment:

Drug: Etentamig

Drug: Daratumumab

Phase 2: Etentamig + Daratumumab Dose B

Experimental group

Description:

Participants will receive etentamig dose B in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.

Treatment:

Drug: Etentamig

Drug: Daratumumab

Phase 2: Etentamig + Daratumumab Dose C

Experimental group

Description:

Participants will receive etentamig dose C in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.

Treatment:

Drug: Etentamig

Drug: Daratumumab

Phase 3: Etentamig + Daratumumab RP3D

Experimental group

Description:

Participants will receive etentamig at the RP3D in combination with daratumumab, as part of the approximately 16 year study duration.

Treatment:

Drug: Etentamig

Drug: Daratumumab

Phase 3: Daratumumab, Lenalidomide, and Dexamethasone (DRd)

Experimental group

Description:

Participants will receive DRd, as part of the approximately 16 year study duration.

Treatment:

Drug: Dexamethasone

Drug: Lenalidomide

Drug: Daratumumab

Drug: Dexamethasone