A Study to Evaluate Adverse Events and Change in Disease Activity With Injected Etentamig Plus Oral Pomalidomide Versus Standard Therapies in Adults With Relapsed or Refractory Multiple Myeloma

A Phase 3, Multicenter, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Etentamig in Combination With Pomalidomide Compared With Standard Available Therapies in Subjects With Relapsed or Refractory Multiple Myeloma (2L+ RRMM)

Multiple myeloma (MM) is a plasma cell malignancy characterized by the proliferation of clonal plasma cells in the bone marrow. The disease primarily localizes to the bones and bone marrow, with resultant cytopenias, bone pain, fractures, infections, hypercalcemia, and renal failure. This study aims to evaluate the safety and change in disease activity of etentamig in combination with pomalidomide compared with standard available therapies in participants with relapsed or refractory multiple myeloma who have received 1-3 prior lines of treatment, including lenalidomide.

Etentamig is an investigational drug being developed for the treatment of relapsed or refractory multiple myeloma. This is a randomized, open-label study. The study will include a safety run-in portion and a randomized portion. The safety run-in participants will receive etentamig in combination with pomalidomide. The randomized portion of the study participants will receive either etentamig with pomalidomide or Standard Available Therapies (SATs). Approximately 520 participants will be enrolled in the study at approximately 200 sites worldwide.

Prior to initiation of the randomized portion of the study, the safety run-in will be conducted in which participants will receive etentamig injections plus oral pomalidomide. Following review of the safety run-in data and per protocol-defined criteria, the study will advance to the randomized portion where participants will be randomized to receive either etentamig injections plus oral pomalidomide or investigator's choice of SAT: SC daratumumab, oral pomalidomide, and oral/ IV dexamethasone (DPd); SC daratumumab, IV carfilzomib, and oral/IV dexamethasone (DKd); or SC teclistamab monotherapy. The total study duration is approximately 75 months

There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab; Drug: Carfilzomib; Drug: Etentamig; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Teclistamab

• Study Type: Interventional
• Enrollment (Estimated): 520
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Wollongong Hospital. /ID# 282694
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital /ID# 283010
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Care - South Brisbane /ID# 282965
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre. /ID# 282692
    • Richmond, Victoria, Australia, 3121
      • Epworth Hospital - Richmond /ID# 281877
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital /ID# 281879
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital /ID# 281881
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
      • British Columbia Cancer Agency Vancouver Centre /ID# 282147
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre - Victoria Hospital & Children's Hospital /ID# 282149
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Universite de Montreal - Hopital Maisonneuve-Rosemont /ID# 281705
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06202
      • Chu de Nice-Hopital Larchet Ii /Id# 283541
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37044
      • CHRU Tours - Hopital Bretonneau /ID# 281925
  • Meurthe-et-Moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54511
      • Centre Hospitalier Regional Universitaire de Nancy - Hopitaux de Brabois /ID# 284303
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • Centre Hospitalier Universitaire de Nantes - L' Hopital l'hotel-Dieu /ID# 282025
  • Provence-Alpes-Côte d'Azur Region
    • Avignon, Provence-Alpes-Côte d'Azur Region, France, 84000
      • Centre Hospitalier d'Avignon /ID# 283509
• Germany
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg /ID# 282874
    • Karlsruhe, Baden-Wurttemberg, Germany, 76133
      • Staedtisches Klinikum Karlsruhe /ID# 283569
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen /ID# 282873
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm /ID# 283884
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Universitaetsklinikum Wuerzburg /ID# 283572
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30459
      • Krh Klinikum Siloah-Oststadt-Heidehaus /ID# 283729
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Universitaetsklinikum Bonn /ID# 283881
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitaetsklinikum Koeln /ID# 283930
• Hungary
  • Vas County
    • Szombathely, Vas County, Hungary, 9700
      • Vas Varmegyei Markusovszky Egyetemi Oktatokorhaz /ID# 283136
• Italy
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 281398
• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum /ID# 283142
    • Rotterdam, South Holland, Netherlands, 3015 CE
      • Erasmus Medisch Centrum /ID# 283408
• Norway
  • Sogn Og Fjordane
    • Bergen, Sogn Og Fjordane, Norway, 5021
      • Haukeland University Hospital /ID# 283524
• Portugal
  • Braga, Portugal, 4710-243
    • 2CA-Braga, Hospital de Braga /ID# 283828
  • Porto, Portugal, 4200-319
    • Unidade Local de Saude Sao Joao /ID# 283530
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1449-005
      • Centro Hospitalar De Lisboa Ocidental - Hospital De Sao Francisco Xavier /ID# 283500
  • Porto District
    • Vila Nova de Gaia, Porto District, Portugal, 4434-502
      • Unidade Local de Saude de Gaia/Espinho /ID# 283492
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 283342
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla /ID# 283344
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona /ID# 283290
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital /ID# 282970
• United Kingdom
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • University Hospitals Plymouth NHS Trust /ID# 283108
  • Edinburgh, City of
    • Edinburgh, Edinburgh, City of, United Kingdom, EH4 2XU
      • Western General Hospital - NHS Lothian /ID# 281838
  • Greater London
    • London, Greater London, United Kingdom, EC1A 7BE
      • St Bartholomews Hospital - Barts Health /ID# 283714
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Queen Alexandra Hospital /ID# 281839
  • North Lanarkshire
    • Airdrie, North Lanarkshire, United Kingdom, ML6 0JS
      • NHS Lanarkshire /ID# 282021
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham City Hospital /ID# 282748
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • University of Arizona Cancer Center /ID# 285339
  • California
    • Cerritos, California, United States, 90703
      • Toi Clinical Research - Whittier /ID# 284462
    • Los Angeles, California, United States, 90095-3075
      • University of California Los Angeles /ID# 282444
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado - Anschutz Medical Campus /ID# 283478
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital /ID# 283734
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida /ID# 283692
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers /ID# 284769
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center /ID# 283095
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center /ID# 285204
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer And Hematology Centers Of Western Michigan - Grand Rapids /ID# 282591
  • New York
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital /ID# 283535
    • New York, New York, United States, 10032
      • Columbia University Medical Center /ID# 283510
    • New York, New York, United States, 10065
      • Weill Cornell Medicine - Cornell University /ID# 283712
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center /ID# 283480
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Lineberger Comprehensive Cancer Center /ID# 281454
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center /ID# 283475
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Forsyth Medical Center /ID# 283485
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center /ID# 283527
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University /ID# 282023
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners /ID# 281380
  • Texas
    • Houston, Texas, United States, 77030-4000
      • MD Anderson Houston /ID# 282622
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute /ID# 283512
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Massey Cancer Center: Dalton Oncology Clinic /ID# 283606
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics /ID# 282516

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of relapsed or refractory (RR) multiple myeloma (MM).
• Prior treatment with at least one and no more than three prior lines of therapy, including lenalidomide.
• Adequate organ function and performance status

Exclusion Criteria:

• Prior B-cell maturation antigen (BCMA) directed T-cell engager therapy (bispecific or trispecific)
• Known central nervous system involvement of MM
• Known history of other active malignancies within the past 3 years (with specific exceptions)
• Clinically significant conditions (renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary, or hepatic disease within the last 6 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In: Etentamig Plus Pomalidomide; Participants will receive etentamig in combination with pomalidomide, as part of the approximately 75 month study duration.	Drug: Etentamig; Injection; Drug: Pomalidomide; Oral
Experimental: Randomized Portion: Etentamig Plus Pomalidomide; Participants will receive etentamig in combination with pomalidomide, as part of the approximately 75 month study duration.	Drug: Etentamig; Injection; Drug: Pomalidomide; Oral
Active Comparator: Randomized Portion: Standard Available Therapy (SAT); Participants will receive Investigator's choice of SATs: DPd, DKd, or teclistamab monotherapy as part of the 75 month study duration.	Drug: Daratumumab; Injection; Drug: Carfilzomib; Injection; Drug: Dexamethasone; Oral or Injection; Drug: Teclistamab; Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-In: Number of Participants With Adverse Events (AE)s	AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.	Up to Approximately 75 Months
Randomized Portion: Complete Response (CR) or Better Rate Per Independent Review Committee (IRC) Assessment	CR or better is defined as proportion of participants with best overall response (BOR) of CR or stringent CR (sCR) as assessed per International Myeloma Working Group (IMWG) 2016 criteria. CR is defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and less than 5% plasma cells in bone marrow aspirates. The treatment effect will be summarized as the difference in the CR or better rates between etentamig in combination with pomalidomide and standard available therapies (SAT).	Up to Approximately 75 Months
Randomized Portion: Progression-Free Survival (PFS) Per Independent Review Committee (IRC) Assessment	PFS is defined as duration from the date of randomization to the date of disease progression assessed according to the IMWG (2016) response criteria, per IRC assessment or death due to any cause, whichever occurs first.	Up to Approximately 75 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-In: Best Overall Response (BOR) of Per Investigator Assessment	BOR is defined as the best response achieved across all response assessments, partial response (PR) + very good partial response (VGPR) + complete response (CR) + stringent complete response (sCR), from randomization until disease progression per investigator assessment, using IMWG (2016) response criteria.	Up to Approximately 75 Months
Safety Run-In: Maximum Observed Concentration (Cmax) of Etentamig	Cmax of Etentamig.	Up to Approximately 12 Months
Safety Run-In: Time to Cmax (Tmax) of Etentamig	Cmax of Etentamig.	Up to Approximately 12 Months
Safety Run-In: Area under the Serum Concentration-Time Curve (AUC) of Etentamig	Cmax of Etentamig.	Up to Approximately 12 Months
Safety Run-In: Immunogenicity of Etentamig	Immunogenicity of etentamig is defined as the summary of antidrug antibody (ADA) status, ADA titers, and neutralizing antibody (NAb)s, if NAb samples are analyzed.	Up to Approximately 75 Months
Randomized Portion: Minimal Residual Disease Negative Complete Response (MRDnegCR) Per IRC Assessment	MRDnegCR is defined as achievement of CR or better by IMWG (2016) response criteria per IRC assessment and MRD negative status as assessed by next-generation sequencing (NGS) at threshold defined in the protocol.	Up to Approximately 75 Months
Randomized Portion: Overall Survival (OS)	Overall Survival (OS) is defined as the duration from the date of randomization to the date of death from any cause.	Up to Approximately 75 Months
Randomized Portion: Sustained Minimal Residual Disease (MRD) Negativity	Sustained MRD negativity assessed in participants with relapsed/refractory multiple myeloma (RRMM).	Up to Approximately 75 Months
Randomized Portion: Best Minimal Residual Disease Negative Complete Response (MRD Negative CR) Per IRC Assessment	Best MRD negative CR per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM).	Up to Approximately 75 Months
Randomized Portion: BOR Per IRC Assessment	BOR is defined as the best response achieved across all response assessments, PR + VGPR + CR +sCR from randomization until disease progression per IRC assessment, using IMWG (2016) response criteria.	Up to Approximately 75 Months
Randomized Portion: VGPR or Better Rate Per IRC Assessment	VGPR or better rate per IRC assessment, defined as percentage of participants achieving VGPR, CR, or sCR using IMWG (2016) response criteria.	Up to Approximately 75 Months
Randomized Portion: Time to Response (TTR) Per IRC Assessment	TTR is defined as the time from randomization to first documented response (PR or better) per IRC assessment using IMWG (2016) response criteria.	Up to Approximately 75 Months
Randomized Portion: Duration of Response (DOR) Per IRC Assessment	DOR is defined as the time from first documented response (PR or better) to disease progression or death, whichever occurs first, per IRC assessment using IMWG (2016) response criteria.	Up to Approximately 75 Months
Randomized Portion: Second Progression-Free Survival (PFS2)	PFS2 is defined as time from randomization to second disease progression or death from any cause, whichever occurs first.	Up to Approximately 75 Months
Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (QoL) Score	Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life score. Patient-reported outcome (PRO) assessment.	Up to Approximately 75 Months
Randomized Portion: Event-Free Survival (EFS) Per IRC Assessment	EFS per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM).	Up to Approximately 75 Months
Randomized Portion: Time to Next Treatment (TTNT)	TTNT is defined as time from randomization to initiation of next anti-myeloma therapy.	Up to Approximately 75 Months
Randomized Portion: Time to Symptomatic Disease Progression	Time to symptomatic disease progression in participants with relapsed/refractory multiple myeloma (RRMM).	Up to Approximately 75 Months
Randomized Portion: Change From Baseline in Disease Symptoms as Measured by the Disease Symptoms Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Myeloma Module (EORTC QLQ-MY20)	Change from baseline in disease symptoms as measured by the disease symptoms domain of the EORTC QLQ-MY20 .	Up to Approximately 75 Months
Randomized Portion: Change From Baseline in Physical Functioning as Measured by the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	Change from baseline at 6 months in physical functioning as measured by the physical functioning domain of the EORTC QLQ-C30.	Up to Approximately 75 Months
Randomized Portion: Overall Bother Due to Treatment Side Effects as Assessed by the Functional Assessment of Cancer Therapy - General Population, Item 5 (FACT-G GP5)	Overall bother due to treatment side effects as assessed by the Functional Assessment of Cancer Therapy - General Population, Item 5 FACT-G GP5. Patient-reported outcome (PRO) assessment.	Up to Approximately 75 Months

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): February 1, 2033
• Study Completion (Estimated): February 1, 2033

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pomalidomide; Cancer; Relapsed or Refractory Multiple Myeloma; Etentamig
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasms; Recurrence; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; carfilzomib; pomalidomide; daratumumab
• Other Study ID Numbers: M22-538; 2026-525596-11-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes