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.

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.