Study to Evaluate Change in Disease Activity and Adverse Events of Subcutaneous Etentamig Compared With Daratumumab Plus Cyclophosphamide Plus Bortezomib Plus Dexamethasone (Dara-CyBorD) in Adults With Amyloid Light Chain (AL) Amyloidosis

NCT07793422 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: M24-4732026-525253-37-00
• Study Type: interventional
• Target: 370
• Locations: 0 countries
• Sites: N/A

Brief Summary

Amyloid light chain (AL) amyloidosis is a rare disease caused by abnormal plasma cells producing misfolded light chain proteins that deposit in organs, leading to organ dysfunction and failure. The goal of this study is to evaluate the safety and efficacy of etentamig compared to daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in participants with newly diagnosed AL amyloidosis. Etentamig is an investigational drug being developed for the treatment of newly diagnosed AL amyloidosis. This is an open-label study. The study consists of 2 parts: a Safety Run-in where participatns will receive etentamig, and a Randomized Portion with 2 treatment arms where participants will receive etentamig, or Dara-CyBorD. Approximately 370 participants will be enrolled in the study at approximately 130 sites worldwide. Participants will receive injected etentamig, in the Safety Run-in. Participants will receive injected etentamig, or Dara-CyBorD per the local label, in the Randomized Portion of the study. The total study duration is approximately 96 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.

Conditions

Amyloid Light Chain (AL) Amyloidosis

Keywords

Amyloid Light Chain Amyloidosis, Newly Diagnosed AL Amyloidosis, Etentamig, ABBV-383, VCd

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. Safety and tolerability assessed through adverse events, laboratory tests, vital signs, physical examinations, and other safety assessments.

  Up to Approximately 96 Months

• Randomized Portion: Complete Hematologic Response (HemeCR) Rate

  HemeCR rate is defined as the proportion of subjects with the best overall response of hemeCR as determined by International Amyloidosis Consensus Criteria (IACC) and assessed by the independent review committee (IRC)

  Up to Approximately 60 Months

• Randomized Portion: Major Organ Deterioration Progression-Free Survival (MOD-PFS)

  MOD-PFS is defined as the time from the date of randomization to the date of MOD-PFS event or death from any cause, whichever occurs first. MOD-PFS includes: Development of hematologic progressive disease per consensus guidelines or high-risk difference in free light chain (dFLC) progression; Clinical manifestation of cardiac failure (defined as need for cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); Clinical manifestation of renal failure (defined as development of end-stage renal disease needing hemodialysis or renal transplant); Death. MOD-PFS will be assessed by an Independent Review Committee.

  Up to Approximately 60 Months

Secondary Outcomes (27)

• Safety Run-In: Major Organ Deterioration Progression-Free Survival (MOD-PFS)

  Up to Approximately 60 Months

• Safety Run-In and Randomized Portion: Overall Survival (OS)

  Up to Approximately 60 Months

• Safety Run-In and Randomized Portion: Percentage of Participants With Hematologic Very Good Partial Response (VGPR) or Better

  Up to Approximately 60 Months

• Safety Run-In and Randomized Portion: Cardiac Response Rate

  Up to Approximately 60 Months

• Safety Run-In and Randomized Portion: Renal Response Rate

  Up to Approximately 60 Months

Study Arms (3)

Safety Run-in: Etentamig

EXPERIMENTAL

Participants receive etentamig, as part of a 96 month study duration.

Drug: Etentamig

Randomized Portion: Etentamig

EXPERIMENTAL

Participants will receive etentamig , as part of a 96 month study duration.

Drug: Etentamig

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone

ACTIVE COMPARATOR

Participants will receive daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in accordance with the local approved label, as part of a 96 month study duration..

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Etentamig DRUG

Injection

Randomized Portion: Etentamig; Safety Run-in: Etentamig

Daratumumab DRUG

Injection

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone

Cyclophosphamide DRUG

Oral

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone

Bortezomib DRUG

Injection

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone

Dexamethasone DRUG

Oral

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red-stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance.
• Evidence of a monoclonal plasma cell proliferative disorder (serum or urine monoclonal protein, abnormal free light-chain ratio, or clonal plasma cells in the bone marrow).
• Measurable disease of amyloid light chain (AL) amyloidosis as defined by difference in free light chains (dFLC) \>= 50 mg/L
• No history of treatment with anti-amyloidosis therapy.
• Presence of an amyloid-related systemic syndrome with at least 1 organ impacted by AL amyloidosis according to International Myeloma Working Group (IMWG) diagnostic criteria.
• Considered AL amyloidosis cardiac risk stage 1, 2, or 3a (or 3b \[randomized portion only\]).
• Eastern Cooperative Oncology Group performance status \<= 2.

You may not qualify if:

• Known allergic reaction, significant sensitivity, or intolerance to constituents of the study treatments.
• Active hepatitis B or hepatitis C infection.
• History of other active malignancies within the past 3 years (with specified exceptions).

Sponsors & Collaborators

• AbbVie: lead

MeSH Terms

Conditions

Amyloidosis; Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; Cyclophosphamide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): November 29, 2026
• Primary Completion (Estimated): December 1, 2034
• Study Completion (Estimated): December 1, 2034
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/
• Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/