Immunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis has many root causes and is characterized by the overproduction of AL that are secreted by clonal bone marrow plasma cells. This is a study to determine adverse events and change in disease activity in adult participants with AL amyloidosis treated with ABBV-383.

Etentamig (ABBV-383) is an investigational drug being developed for the treatment of AL amyloidosis. This study in broken into 2 parts (dose escalation and dose expansion) with 4 arms. During dose escalation (arms 1-3) participants will receive 1 of 3 doses of ABBV-383 to determine the part 2 dose. After completion of the dose escalation portion of the study, the dose expansion (part 2) portion of the study will begin. One arm (arm 4) will begin and participants will receive a dose determined during the dose escalation portion (part 1). Around 76 adult participants with relapsed/refractory AL amyloidosis will be enrolled at approximately 25 sites across the world.

Participants will receive Etentamig (ABBV-383) as an infusion into the vein for up to approximately 2 year study duration.

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.

Inclusion Criteria:

• Diagnosis of primary systemic immunoglobulin light chain (AL) amyloidosis.
• Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
• Have at least 1 organ historically impacted by AL amyloidosis.
• Considered AL amyloidosis cardiac risk stage 1, 2, or 3a, or considered risk stage 3b with stable cardiac function and markers for 3 months prior to dosing, and have measurable disease of AL amyloidosis as defined by difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L or meeting high-risk dFLC progression criteria after immediate prior line of therapy.
• Has previously been exposed to a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.

Exclusion Criteria:

• Known history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.

• Known allergic reaction, significant sensitivity, or intolerance to constituents of the study treatment (and excipients) and/or other products in the same class.

• Participant has the following conditions:

  • Other non-AL amyloid disease;
  • Previous or current diagnosis of symptomatic multiple myeloma (MM), including the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells in the bone marrow, or hypercalcemia (defined as corrected calcium > 11 mg/dL);
  • Active plasma cell leukemia (i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential);
  • Waldenström's macroglobulinemia;
  • Acute diffuse infiltrative pneumopathy;
  • Major surgery within 28 days prior first dose or planned during study participation;
  • History of organ transplant requiring continued use of immunosuppressants;
  • Acute infections within 14 days prior first dose requiring parenteral therapy (antibiotic, antifungal, or antiviral);
  • Participant has received an autologous stem cell transplant (SCT) within 12 weeks or an allogeneic SCT within 1 year of the first dose of study treatments.