A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused Etentamig (ABBV-383) in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma

A Dose Escalation and Expansion Study of Etentamig (ABBV-383) in Combination With Anti-Cancer Regimens for the Treatment of Patients With Newly Diagnosed or Relapsed/Refractory Multiple Myeloma

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of etentamig (ABBV-383) when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), or daratumumab-dexamethasone (Dd), in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed.

Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Etentamig co-administered with Pd, Rd, or Dd, will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of etentamig, followed by a dose expansion phase to confirm the dose. Approximately 320 adult participants with R/R MM will be enrolled in the study in approximately 48 sites worldwide.

Participants will receive intravenous (IV) etentamig co-administered with oral/IV Pd, oral/IV Rd, or oral/IV/subcutaneous (SC) Dd in 28-day cycles.

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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Pomalidomide; Drug: Lenalidomide; Drug: Daratumumab; Drug: Etentamig

• Study Type: Interventional
• Enrollment (Actual): 283
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital /ID# 243740
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle /ID# 243730
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health - Monash Medical Centre /ID# 244403
    • Fitzroy Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 256879
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Ctr /ID# 256880
    • Richmond, Victoria, Australia, 3121
      • Epworth Healthcare /ID# 243734
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital /ID# 244753
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 242819
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf /ID# 243141
  • Regensburg, Germany, 93042
    • Universitaetsklinikum Regensburg /ID# 242837
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen /ID# 242815
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Universitaetsklinikum Wuerzburg /ID# 242826
• Italy
  • Bologna, Italy, 40138
    • IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 242581
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico /ID# 244057
  • Milano
    • Milan, Milano, Italy, 20132
      • IRCCS Ospedale San Raffaele /ID# 242583
  • Reggio Emilia
    • Meldola, Reggio Emilia, Italy, 47014
      • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 242584
  • Roma
    • Rome, Roma, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita Cattolica /ID# 242582
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Nagoya City University Hospital /ID# 249094
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 245889
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital /ID# 245966
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital /ID# 246812
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 701-1192
      • Okayama Medical Center /ID# 245882
  • Yamagata
    • Yamagata, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 245888
• Poland
  • Lower Silesian Voivodeship
    • Opole, Lower Silesian Voivodeship, Poland, 45-372
      • Szpital Wojewodzki w Opolu sp. z o.o. /ID# 243954
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny We Wrocławiu /ID# 243246
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-081
      • Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie /ID# 243500
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne /ID# 243249
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 242976
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 242978
  • Madrid, Spain, 28027
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 244145
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 242975
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio /ID# 242974
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Duran i Reynals /ID# 242979
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona /ID# 242977
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences /ID# 243096
  • Florida
    • Miami, Florida, United States, 33136-1002
      • Sylvester Comprehensive Cancer Center /ID# 243673
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center /ID# 243437
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore /ID# 243679
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 249529
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts - Worcester /ID# 243977
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 243438
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital /ID# 243829
  • New York
    • New York, New York, United States, 10029-6030
      • Rutenberg Cancer Center /ID# 244647
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center /ID# 244656
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Levine Cancer Institute /ID# 242851
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • University of Texas Southwestern Medical Center /ID# 243273
  • Utah
    • Salt Lake City, Utah, United States, 84112-5500
      • Huntsman Cancer Institute /ID# 242872
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington /ID# 243172
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Froedtert Memorial Lutheran Hospital /ID# 242654

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance of <= 2.
• Must have confirmed diagnosis of Relapsed/Refractory (R/R) Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.
• Must have measurable disease as determined by central lab as outlined in the protocol.
• Must be naïve to treatment with Etentamig.
• Must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded.
• Arms A, B and C: Participant has received at least 3 prior lines of MM treatment.
• Arm E: Participant has received 1-3 prior lines of MM treatment.

Exclusion Criteria:

• Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study treatment.
• Unresolved adverse event (AE)s >= Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from prior anticancer therapy.

• Has any of the following conditions:

  • Nonsecretory Multiple Myeloma (MM).
  • Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 10^9L circulating plasma cells by standard differential.
  • Waldenstrom's macroglobulinemia.
  • Light chain amyloidosis.
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
  • Major surgery within 4 weeks prior to first dose or planned study participation.
  • Acute infections within 14 days prior to first dose of study requiring therapy (antibiotic, antifungal or antiviral).
  • Uncontrolled diabetes or hypertension within 14 days prior to first dose.
  • Peripheral neuropathy >= Grade 3 or >= Grade 2 with pain within 2 weeks prior to first dose.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone); Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.	Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Pomalidomide; Oral; Capsule; Drug: Etentamig; Intravenous (IV) Infusion; Other Names: ABBV-383
Experimental: Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone); Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.	Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Lenalidomide; Oral; Capsule; Drug: Etentamig; Intravenous (IV) Infusion; Other Names: ABBV-383
Experimental: Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone); Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.	Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Daratumumab; Subcutaneous Injection (SC); Drug: Etentamig; Intravenous (IV) Infusion; Other Names: ABBV-383
Experimental: Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone); Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.	Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Pomalidomide; Oral; Capsule; Drug: Etentamig; Intravenous (IV) Infusion; Other Names: ABBV-383

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	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. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to Approximately 3 Years
Number of Participants with Dose Limiting Toxicities (DLT) of Etentamig	DLT events as described in the protocol will be assessed.	Up to approximately 28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 or death.	Up to Approximately 3 Years
Duration of Response (DOR)	DOR will be defined as the number of days from the date of first response (sCR, CR, VGPR, or PR) to the earliest recurrence, progressive disease, or death, whatever occurs first.	Up to Approximately 3 Years
Time-to-Progression (TTP)	TTP is defined as the number of days from the date of first dose to the date of earliest disease progression.	Up to Approximately 3 Years
Overall Response Rate (ORR)	ORR is defined as partial response (PR) + very good partial response (VGPR) + complete remission (CR) + stringent complete response (sCR); proportion of participants who achieved a PR or better.	Up to Approximately 3 Years
Percentage of Participants with Minimal Residual Diseas (MRD) Negativity by Next-Generation Sequencing (NGS)	MRD negative status (threshold as assessed by NGS Adaptive Clonoseq) with >= CR (per International Myeloma Working Group [IMWG] response criteria) prior to the initiation of new myeloma therapy.	Up to Approximately 3 Years

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): October 20, 2022
• Primary Completion (Estimated): September 1, 2033
• Study Completion (Estimated): September 1, 2033

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pomalidomide; Cancer; Daratumumab; Lenalidomide; Dexamethasone; Relapsed/Refractory Multiple Myeloma; Nirogacestat; ABBV-383; Etentamig
• 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; pomalidomide; daratumumab
• Other Study ID Numbers: M22-947; 2023-506871-88-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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