RecruitingPhase 2Phase 3NCT07095452

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

Phase 2/3, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Subjects With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant


Sponsor

AbbVie

Enrollment

660 participants

Start Date

Jan 8, 2026

Study Type

INTERVENTIONAL

Conditions

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. 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.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • 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 Criteria4

  • 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.

Interventions

DRUGEtentamig

Intravenous (IV) Infusion

DRUGLenalidomide

Oral Capsule

DRUGDaratumumab

Subcutaneous Injection

DRUGDexamethasone

Oral Tablet

DRUGDexamethasone

IV Injection


Locations(25)

Colorado Blood Cancer Institute /ID# 279080

Denver, Colorado, United States

Fort Wayne Medical Oncology And Hematology /ID# 278141

Fort Wayne, Indiana, United States

Minnesota Oncology - Minneapolis Clinic /ID# 278720

Minneapolis, Minnesota, United States

Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 277946

New York, New York, United States

Willamette Valley Cancer Institute and Research Center /ID# 278721

Eugene, Oregon, United States

SCRI Oncology Partners /ID# 278353

Nashville, Tennessee, United States

Texas Oncology - The Woodlands /ID# 278726

The Woodlands, Texas, United States

Texas Oncology - Northeast Texas /ID# 278725

Tyler, Texas, United States

Virginia Cancer Specialists - Fairfax /ID# 278716

Fairfax, Virginia, United States

Blue Ridge Cancer Care - Roanoke /ID# 278722

Roanoke, Virginia, United States

Centre Hospitalier Annecy Genevois /ID# 278406

Epagny Metz Tessy, Auvergne-Rhône-Alpes, France

Chu De Lille - Hopital Claude Huriez /ID# 278413

Lille, Hauts-de-France, France

Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 278402

Nantes, Pays de la Loire Region, France

Centre Hospitalier Universitaire de Saint Etienne - Hopital Nord /ID# 278421

St-Priest-en-Jarez, Pays de la Loire Region, France

Nagoya City University Hospital /ID# 278188

Nagoya, Aichi-ken, Japan

Matsuyama Red Cross Hospital /ID# 278660

Matsuyama, Ehime, Japan

Tokai University Hospital /ID# 278157

Isehara, Kanagawa, Japan

University Hospital Kyoto Prefectural University of Medicine /ID# 278156

Kyoto, Kyoto, Japan

Hospital Universitario de Gran Canaria Doctor Negrín /ID# 278527

Las Palmas de Gran Canaria, Las Palmas, Spain

Complejo Asistencial Universitario de León - Hospital de León /ID# 278534

León, Leon, Spain

Clinica Universidad de Navarra - Pamplona /ID# 278583

Pamplona, Navarre, Spain

Hospital Clinic de Barcelona /ID# 278532

Barcelona, Spain

Hospital Universitario Ramón y Cajal /ID# 278533

Madrid, Spain

Hospital Universitario de Salamanca /ID# 278530

Salamanca, Spain

Hospital Universitari i Politècnic La Fe /ID# 278525

Valencia, Spain

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NCT07095452


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