RecruitingInterventionalPhase 2/Phase 3

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

NCT ID: NCT07095452Sponsor: AbbVieLast updated: 2026-06-11

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.

Arms & interventions

DrugEtentamig
Intravenous (IV) Infusion
DrugLenalidomide
Oral Capsule
DrugDaratumumab
Subcutaneous Injection
DrugDexamethasone
Oral Tablet
DrugDexamethasone
IV Injection

Outcome measures

Primary

Phase 2 and 3: Percentage of Participants with Adverse Events (AE)s
An AE 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.
Time frame: Up to Approximately 16 Years
Phase 2: Change in Clinical Activity
Clinical activity is defined as change in response rates \[Overall Response Rate (ORR), Complete Response (CR) or Better, Very Good Partial Response (VGPR), Partial Response (PR)\] as determined International Myeloma Working Group (IMWG (2016).
Time frame: Up to Approximately 52 weeks
Phase 3: Minimal Residual Disease (MRD) Negative CR Rate
MRDnegCR rate, is defined as the percentage of participants who have achieved stringent complete response (sCR) or CR as assessed by independent review committee (IRC) and have negative MRD defined at 10\^-5 threshold as assessed by next generation sequencing (NGS).
Time frame: Up to Approximately 52 weeks
Phase 3: Progression-Free Survival (PFS)
PFS is defined as the duration from the date of randomization to the date of confirmed disease progression (PD) determined by IRC per IMWG (2016) response criteria, or death, whichever occurs first.
Time frame: Up to Approximately 130 Months

Secondary

Phase 2: MRD Negative CR Rate
Time frame: Up to Approximately 52 Weeks
Phase 2: PFS
Time frame: Up to Approximately 130 Months
Phase 2: Sustained MRD Negativity Rate
Time frame: Up to Approximately 12 Months
Phase 2: Area Under the Serum Concentration-Time Curve (AUC)
Time frame: Up to Approximately 12 Months
Phase 2: Overall Survival (OS)
Time frame: Up to Approximately 16 Years
Phase 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Time frame: Up to Approximately 16 Years
Phase 2: Maximum Observed Serum Concentration (Cmax)
Time frame: Up to Approximately 12 Months
Phase 2: Time to Cmax (Time to Maximum Observed Concentration, Tmax)
Time frame: Up to Approximately 12 Months
Phase 2: Positive Anti-Drug Antibodies (ADAs)
Time frame: Up to Approximately 90 days after the last dose of study treatment
Phase 2: Negative ADAs
Time frame: Up to Approximately 90 days after the last dose of study treatment
Phase 2: Neutralizing Anti-Drug Antibodies (NAbs)
Time frame: Up to Approximately 90 days after the last dose of study treatment
Phase 3: OS
Time frame: Up to Approximately 16 Years
Phase 3: Sustained MRD Negativity Rate
Time frame: Up to Approximately 12 Months
Phase 3: Rate of >= CR
Time frame: Up to Approximately 12 Months
Phase 3: Rate of >= VGPR or Better
Time frame: Up to Approximately 12 Months
Phase 3: ORR
Time frame: Up to Approximately 52 Weeks
Phase 3: Time to Response (TTR)
Time frame: Up to Approximately 12 Months
Phase 3: Duration of Response (DOR)
Time frame: Up to Approximately 16 Years
Phase 3: Time-to-Progression (TTP)
Time frame: Up to Approximately 16 Years
Phase 3: Event Free Survival (EFS)
Time frame: Up to Approximately 16 Years
Phase 3: Progression-Free Survival on Subsequent Therapy (PFS2)
Time frame: Up to Approximately 16 Years
Phase 3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Time frame: Up to Approximately 16 Years
Phase 3: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Functioning Score
Time frame: Up to Approximately 16 Years
Phase 3: Change from Baseline in EORTC QLQ-C30 Global Health Status/QoL Score
Time frame: Up to Approximately 16 Years
Phase 3: Change from Baseline and Time to Deterioration in the Remaining Scales and Items of EORTC QLQ-C30
Time frame: Up to Approximately 16 Years
Phase 3: Symptomatic AEs as Assessed by the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: Up to Approximately 16 Years
Phase 3: Overall Bother Due to Treatment Side Effects as Assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) GP5
Time frame: Up to Approximately 16 Years
Phase 3: Change from Baseline in Patient Global Impression of Severity (PGIS) Scores
Time frame: Up to Approximately 16 Years
Phase 3: Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Scores
Time frame: Up to Approximately 16 Years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (17)

Mayo Clinic Hospital Scottsdale /ID# 278349

Scottsdale, Arizona, 85259

Recruiting

Cedars-Sinai Medical Center /ID# 278238

Los Angeles, California, 90048

Recruiting

Colorado Blood Cancer Institute /ID# 279080

Denver, Colorado, 80218

Recruiting

Winship Cancer Institute of Emory University /ID# 277667

Atlanta, Georgia, 30322

Recruiting

Fort Wayne Medical Oncology And Hematology /ID# 278141

Fort Wayne, Indiana, 46804

Recruiting

Minnesota Oncology - Minneapolis Clinic /ID# 278720

Minneapolis, Minnesota, 55404

Recruiting

Mayo Clinic Hospital Rochester /ID# 277886

Rochester, Minnesota, 55905

Recruiting

Icahn School of Medicine at Mount Sinai /ID# 277844

New York, New York, 10029

Recruiting

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

New York, New York, 10065

Recruiting

Weill Cornell Medicine Myeloma Center /ID# 278216

New York, New York, 10065

Recruiting

University of North Carolina at Chapel Hill /ID# 277708

Chapel Hill, North Carolina, 27514

Recruiting

Willamette Valley Cancer Institute and Research Center /ID# 278721

Eugene, Oregon, 97401

Recruiting

SCRI Oncology Partners /ID# 278353

Nashville, Tennessee, 37203

Recruiting

Texas Oncology - The Woodlands /ID# 278726

The Woodlands, Texas, 77380

Recruiting

Texas Oncology - Northeast Texas /ID# 278725

Tyler, Texas, 75702

Recruiting

Virginia Cancer Specialists - Fairfax /ID# 278716

Fairfax, Virginia, 22031

Recruiting

Blue Ridge Cancer Care - Roanoke /ID# 278722

Roanoke, Virginia, 24014

Recruiting