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

A Phase 3 Multicenter, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Etentamig (ABBV-383) Compared to Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (Dara-CyBorD) in Subjects With Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyloid Light Chain (AL) Amyloidosis
• Intervention / Treatment: Drug: Daratumumab; Drug: Dexamethasone; Drug: Etentamig; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 370
• Phase: Phase 3

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-in: Etentamig; Participants receive etentamig, as part of a 96 month study duration.	Drug: Etentamig; Injection
Experimental: Randomized Portion: Etentamig; Participants will receive etentamig , as part of a 96 month study duration.	Drug: Etentamig; Injection
Active Comparator: Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone; 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; Injection; Drug: Dexamethasone; Oral; Drug: Cyclophosphamide; Oral; Drug: Bortezomib; Injection; Drug: Bortezomib; Infusion; Drug: Cyclophosphamide; Infusion; Drug: Dexamethasone; Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-In: 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.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Overall Survival (OS)	Overall survival defined as the time from randomization to death from any cause.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Percentage of Participants With Hematologic Very Good Partial Response (VGPR) or Better	Percentage of participants achieving hematologic very good partial response or better based on International Amyloidosis Consensus Criteria.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Cardiac Response Rate	Percentage of participants achieving cardiac response as assessed per graded criteria.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Renal Response Rate	Percentage of participants achieving renal response as assessed per the International Amyloidosis Consensus Criteria (IACC) criteria.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Liver Response Rate	Percentage of participants achieving liver response as assessed per the International Amyloidosis Consensus Criteria (IACC) criteria.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Next Treatment	Time from randomization to initiation of next anti-AL amyloidosis treatment.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Complete Hematologic Response	Time from randomization to first documentation of complete hematologic response (hemeCR) as determined by International Amyloidosis Criteria Committee.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Duration of Complete Hematologic Response	Duration of complete hematologic response (hemeCR) defined as the time from first documentation of hemeCR to the date of loss of hemeCR.	Up to Approximately 60 Months
Randomized Portion: Time to Cardiac Response	Time from randomization to first achievement of cardiac response.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Renal Response	Time from randomization to first achievement of renal response.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Liver Response	Time from randomization to first achievement of liver response.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Duration of Cardiac Response	Time from first achievement of cardiac response to cardiac progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Duration of Renal Progression	Time from first achievement of renal response to renal progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Duration of Liver Response	Time from first achievement of liver response to liver progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Cardiac Progression	Time from randomization to first occurrence of cardiac progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Renal Progression	Time from randomization to first occurrence of renal progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Liver Progression	Time from randomization to first occurrence of liver progression.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Maximum Serum Concentration (Cmax) of Etentamig	Cmax of etentamig.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Time to Maximum Serum Concentration (Tmax) of Etentamig	Tmax of etentamig.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Area Under the Concentration-Time Curve (AUC) of Etentamig	AUC of etentamig.	Up to Approximately 60 Months
Safety Run-In and Randomized Portion: Percentage of Participants With Anti-Drug Antibodies (ADA)	Immunogenicity assessed through summary of antidrug antibody (ADA) status, ADA titers, and neutralizing antidrug antibodies (NAbs), if NAbs samples are analyzed.	Up to Approximately 60 Months
Randomized Portion: Change from Baseline in Physical Functioning as Measured by 36-Item Short Form Health Survey Version 2 (SF-36 v2) Physical Component Summary Score	The SF-36 v2 is a 36-item questionnaire measuring health-related quality of life across eight domains. Higher scores indicate better health status.	Up to Approximately 60 Months
Randomized Portion: Change from Baseline in Mental Functioning as Measured by SF-36 v2 Mental Component Summary Score	The SF-36 v2 is a 36-item questionnaire measuring health-related quality of life across eight domains. Higher scores indicate better health status.	Up to Approximately 60 Months
Randomized Portion: Change from Baseline in Health-Related Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Fatigue Scale Score	The EORTC QLQ-C30 is a 30-item questionnaire assessing cancer-specific quality of life. Higher scores indicate worse symptoms.	Up to Approximately 60 Months
Randomized Portion: Change from Baseline in Fatigue as Measured by EORTC QLQ-C30 Fatigue Scale Score	The EORTC QLQ-C30 is a 30-item questionnaire assessing cancer-specific quality of life. Higher scores indicate worse symptoms.	Up to Approximately 60 Months
Randomized Portion: Change from Baseline in Disease Symptoms as Measured by Additional EORTC Questionnaire Symptom Scales/Items	The EORTC questionnaires assess cancer-specific symptoms and quality of life.	Up to Approximately 60 Months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): November 29, 2026
• Primary Completion (Estimated): December 1, 2034
• Study Completion (Estimated): December 1, 2034

Study Registration Dates

• First Submitted: August 26, 2026
• First Submitted That Met QC Criteria: August 26, 2026
• First Posted (Actual): August 28, 2026

Study Record Updates

• Last Update Posted (Actual): August 28, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Amyloid Light Chain Amyloidosis, Newly Diagnosed AL Amyloidosis, Etentamig, ABBV-383, VCd
• Additional Relevant MeSH Terms: Neoplasms; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Paraproteinemias; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Dexamethasone; Cyclophosphamide; daratumumab
• Other Study ID Numbers: M24-473; 2026-525253-37-00 (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.: No