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.

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).