A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-specific Antibodies Intravenously (IV)/Subcutaneously (SC) Alone or in Combinations

A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of T Cell Engaging Bi/Tri-specific Antibodies in Subjects With MM

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 and ABBV-2001 in adult participants with MM.

Etentamig and ABBV-2001 are investigational drugs being developed for the treatment of MM. This study is broken into 6 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants in substudies 1-4 will receive escalating doses of etentamig alone or with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R), followed by etentamig at the dose levels established during the escalation phases alone or with DR, Kd, R. Participants in substudies 1-4 can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Participants in substudies 5-6 will receive escalating doses or at the dose levels established during the escalation phases of ABBV-2001 with iberdomide or mezigdomide. Around 602 adult participants with MM will be enrolled at approximately 75 sites worldwide

In substudies 1-3, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or with IV and DRd, DKd, or R. In substudie 4, participants will receive escalating doses of etentamig as Intravenous (IV) infusions followed by IV infusions of etentamig at the dose levels established during the escalation phase. In substudies 5-6, participants will receive escalating doses of ABBV-2001 as subcutaneous (SC) injections, with oral iberdomide or mezigdomide, followed by SC injections of ABBV-2001 at the dose levels established during the escalation phases with oral iberdomide or mezigdomide. 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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone; Drug: Carfilzomib; Drug: Etentamig; Drug: Dexamethasone; Drug: Iberdomide; Drug: ABBV-2001; Drug: Mezigdomide

• Study Type: Interventional
• Enrollment (Estimated): 602
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Recruiting
      • Coffs Harbour Health Campus /ID# 272010
    • Port Macquarie, New South Wales, Australia, 2444
      • Recruiting
      • Port Macquarie Base Hospital /ID# 275925
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital /ID# 271880
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Icon Cancer Care - South Brisbane /ID# 271836
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital /ID# 272629
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital - Melbourne /ID# 276451
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre. /ID# 272024
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Recruiting
      • The Perth Blood Institute - West Perth /ID# 272469
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus- Haifa /ID# 271364
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center-Hebrew University /ID# 271362
  • Central District
    • Petah Tikva, Central District, Israel, 4941492
      • Recruiting
      • Rabin Medical Center. /ID# 271365
  • Southern District
    • Beersheba, Southern District, Israel, 8410101
      • Recruiting
      • Soroka Medical Center /ID# 271367
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 271366
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Recruiting
      • Nagoya City University Hospital /ID# 273529
  • Kyoto
    • Kyoto, Kyoto, Japan, 602-8566
      • Recruiting
      • University Hospital Kyoto Prefectural University of Medicine /ID# 275713
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Recruiting
      • The University of Osaka Hospital /ID# 275791
      • Contact: Site Coordinator; Phone Number: +81 6-6879-5111
• Norway
  • Oslo, Norway, 0450
    • Recruiting
    • Oslo Universitetssykehus Ulleval /ID# 277915
    • Contact: Site Coordinator; Phone Number: +4722118080
• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Recruiting
    • University Hospitals Birmingham NHS Foundation Trust /ID# 274620
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales /ID# 273446
  • England
    • London, England, United Kingdom, W12 0HS
      • Recruiting
      • Hammersmith Hospital /ID# 274615
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center /ID# 273132
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope - Orange County Lennar Foundation Cancer Center /ID# 277911
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute /ID# 273129
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center /ID# 272628
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University /ID# 274830
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College /ID# 272517
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai - The Tisch Cancer Institute /ID# 272470
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill /ID# 274667
    • Charlotte, North Carolina, United States, 28204-2990
      • Recruiting
      • Atrium Health Levine Cancer Institute /ID# 276193
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health Wake Forest Baptist Medical Center /ID# 274847
  • Ohio
    • Cincinnati, Ohio, United States, 45252
      • Recruiting
      • Oncology Hematology Care - Blue Ash /ID# 272918
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University /ID# 271336
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • University of Texas - Southwestern Medical Center /ID# 274360
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute /ID# 272575

Participation Criteria

Eligibility Criteria

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

Description

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.

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

21

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1: Etentamig Dose Escalation; Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Daratumumab; Subcutaneous Injection; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 1: Etentamig Dose Expansion Dose Level 1; Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Daratumumab; Subcutaneous Injection; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 1: Etentamig Dose Expansion Dose Level 2; Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Daratumumab; Subcutaneous Injection; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 1: Comparator; Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Daratumumab; Subcutaneous Injection; Drug: Dexamethasone; Oral; Drug: Dexamethasone; IV Injection
Experimental: Substudy 2: Etentamig Dose Escalation; Participants will receive escalating etentamig, as part of the approximately 130 month study duration.	Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 2: Etentamig Dose Expansion Dose Level 1; Participants will receive dose level 1 of etentamig, as part of the approximately 130 month study duration.	Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 2: Etentamig Dose Expansion Dose Level 2; Participants will receive dose level 2 of etentamig, as part of the approximately 130 month study duration.	Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 2: Comparator; Participants will receive lenalidomide (R), as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral
Experimental: Substudy 3: Etentamig Dose Escalation; Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration.	Drug: Dexamethasone; Oral; Drug: Carfilzomib; IV Infusion; Drug: Etentamig; Intravenous (IV) Infusion; Drug: Dexamethasone; IV Injection
Experimental: Substudy 3: Etentamig Dose Expansion Dose Level 1; Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration.	Drug: Dexamethasone; Oral; Drug: Carfilzomib; IV Infusion; Drug: Etentamig; Intravenous (IV) Infusion; Drug: Dexamethasone; IV Injection
Experimental: Substudy 3: Etentamig Dose Expansion Dose Level 2; Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration.	Drug: Dexamethasone; Oral; Drug: Carfilzomib; IV Infusion; Drug: Etentamig; Intravenous (IV) Infusion; Drug: Dexamethasone; IV Injection
Experimental: Substudy 3: Comparator; Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration.	Drug: Daratumumab; Subcutaneous Injection; Drug: Dexamethasone; Oral; Drug: Carfilzomib; IV Infusion; Drug: Dexamethasone; IV Injection
Experimental: Substudy 4: Etentamig Dose Escalation; Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 4: Etentamig Dose Expansion Dose Level 1; Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 4: Etentamig Dose Expansion Dose Level 2; Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration.	Drug: Lenalidomide; Oral; Drug: Etentamig; Intravenous (IV) Infusion
Experimental: Substudy 5: ABBV-2001 Dose Escalation; Participants will receive escalating ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.	Drug: Iberdomide; Oral; Drug: ABBV-2001; subcutaneous (SC) Injection
Experimental: Substudy 5: ABBV-2001 Dose Expansion Dose Level 1; Participants will receive dose level 1 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.	Drug: Iberdomide; Oral; Drug: ABBV-2001; subcutaneous (SC) Injection
Experimental: Substudy 5: ABBV-2001 Dose Expansion Dose Level 2; Participants will receive dose level 2 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.	Drug: Iberdomide; Oral; Drug: ABBV-2001; subcutaneous (SC) Injection
Experimental: Substudy 6: ABBV-2001 Dose Escalation; Participants will receive escalating ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.	Drug: ABBV-2001; subcutaneous (SC) Injection; Drug: Mezigdomide; Oral
Experimental: Substudy 6: ABBV-2001 Dose Expansion Dose Level 1; Participants will receive dose level 1 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.	Drug: ABBV-2001; subcutaneous (SC) Injection; Drug: Mezigdomide; Oral
Experimental: Substudy 6: ABBV-2001 Dose Expansion Dose Level 2; Participants will receive dose level 2 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.	Drug: ABBV-2001; subcutaneous (SC) Injection; Drug: Mezigdomide; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AE)s	An adverse event 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.	Up to Approximately 130 Months
Substudy 1: Dose-Limiting Toxicity (DLT) of Etentamig + Daratumumab and Lenalidomide (DR) in Participants with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI NDMM)	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 weeks
Substudy 2: DLT of Etentamig Monotherapy as Maintenance in Participants with Transplant-Eligible Newly Diagnosed Multiple Myeloma (TE NDMM)	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 Weeks
Substudy 3: DLT of Etentamig +Carfilzomib and Dexamethasone (Kd) Combination in Participants with Relapsed or Refractory Multiple Myeloma (RR MM)	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 Weeks
Substudy 4: DLT of Etentamig plus Lenalidomide when Given as Maintenance in Participants with TE NDMM	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 Weeks
Substudy 5: DLT of ABBV-2001 in Combination with Iberdomide in Participants with RR MM	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 Weeks
Substudy 6: DLT of ABBV-2001 in Combination with Mezigdomide in Participants with RR MM	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 8 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substudy 1, 2, 3, 4, 5, 6: Complete Response Rate	Complete response rate is defined as complete response (CR), stringent complete response (sCR) as assessed by the international myeloma working group (IMWG) 2016 criteria for MM.	Up to Approximately 1 Year
Substudy 1, 2, 3, 4, 5, 6: Overall Response Rate (ORR)	The ORR is defined as the percentage of participants who achieve a best overall response of confirmed PR or better determined by IMWG criteria, prior to the initiation of subsequent myeloma therapy.	Up to Approximately 1 Year
Substudy 1, 2, 3, 4, 5, 6: Progression Free Survival (PFS)	PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IMWG) or death.	Up to Approximately 130 Months
Substudy 1, 2, 3, 4, 5, 6: Duration of Response (DOR)	DOR is defined as the time from the date of first response to the earliest occurrence of progressive disease, or death, whatever occurs first.	Up to Approximately 130 Months
Substudy 1, 2, 3, 4, 5, 6: Time-to-Progression (TTP)	TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.	Up to Approximately 130 Months
Substudy 1, 2, 3, 4, 5, 6: Minimal Residual Disease (MRD) negativity	The MRD negativity rate is defined as the proportion of participants who achieve MRD negative status.	Up to Approximately 52 Weeks

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2025
• Primary Completion (Estimated): December 1, 2035
• Study Completion (Estimated): December 1, 2035

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Daratumumab; Lenalidomide; Dexamethasone; Carfilzomib; Iberdomide; Mezigdomide; Multiple Myeloma, Etentamig, ABBV-383, Cancer; ABBV-2001
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Neoplasms; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Dexamethasone; carfilzomib; daratumumab; iberdomide
• Other Study ID Numbers: M25-059; 2024-515770-27-00 (Other Identifier: EU CT)

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.: No