The following criteria is provided for health care professionals.

Inclusion Criteria:

• Participants must have RRMM with measurable disease:
  • Has measurable disease defined as one of the following:
    • Serum M-protein ≥0.5 g/dL (≥5 g/L).
    • Urine M-protein ≥200 mg/24 hours.
    • In participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum free light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100 mg/L), provided serum FLC ratio is abnormal.
• Has undergone stem cell transplant or is considered transplant ineligible.
• Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory, or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 proteasome inhibitor (ie, bortezomib, ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have demonstrated disease progression with the last therapy.
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.

Exclusion Criteria:

• Received treatment with systemic anticancer treatments within 14 days before the first dose of study drug.
• Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of the first dose of TAK-981 and throughout the duration of this trial.
• Prior radiation therapy within 14 days of the first dose of TAK-981.
• Major surgery within 4 weeks before C1D1. participants should be fully recovered from any surgically related complications.
• Plasmapheresis within 28 days of randomization.
• Diagnosis of primary amyloidosis, Waldenström's disease, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), myelodysplastic syndrome, or myeloproliferative syndrome.
• With disease where the only measurable parameter is plasmacytoma.
• Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
• Prior treatment with more than 1 anti-CD38 antibody.
• Requires the use of drugs known to prolong the corrected QT interval (QTc) (during Phase 1b only).
• History of QT interval with Fridericia's correction (QTcF) >480 ms.
• History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C infection.
• Systemic infection requiring systemic antibiotic therapy.
• Active or history pneumonitis.
• Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study drug.
• Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers.
• History of unstable cardiac comorbidities in the following 6 months.