A Study to Evaluate the Safety, Tolerability and Efficacy of Intravenous TAK-573 as Part of Combination Therapy in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)

The purpose of this study is to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of TAK-573 when used with dexamethasone and in combination with bortezomib, pomalidomide, or cyclophosphamide, in participants with RRMM.

The drug that is being tested in this study is called TAK-573. The study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TAK-573 when used in combination with dexamethasone and either bortezomib, pomalidomide or cyclophosphamide in participants with RRMM.

The study will be conducted in 2 phases: Dose Escalation Phase and Dose Expansion Phase. The study will enroll approximately 135 participants (approximately 60 participants in Dose Escalation Phase and approximately 75 participants in Dose Expansion Phase). The dose escalation phase will determine the recommended dose of TAK-573 along with the combination agents for the dose expansion phase.

This multi-center trial will be conducted in the United States, Germany, France, Spain, and Canada. The overall time to participate in this study is approximately 3 years. Participants will be followed up for 30 days after the last dose of study drug for a follow-up assessment.

Eligibility Criteria:
Inclusion Criteria:

1. Received \>=2 prior lines of therapy, including treatment with lenalidomide and a proteasome inhibitor.
2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. With measurable disease, defined as at least 1 of the following:

   * Serum M protein \>=500 mg/dL (\>=5 gram per liter \[g/L\]) on serum protein electrophoresis (SPEP).
   * Urine M protein \>=200 mg/24 hours on urine protein electrophoresis (UPEP).
   * Serum FLC assay result with an involved FLC level \>=10 mg/dL (\>=100 milligram per liter \[mg/L\]), provided the serum FLC ratio is abnormal.
4. Has adequate organ function as determined by the following laboratory values:

   * Absolute neutrophil count (ANC) \>=1000 per cubic millimeter (/mm\^3) (\>=1.0\*10\^9 \[per liter\]/L)
   * Platelets \>=75,000/mm\^3 (\>=75\*10\^9/L)
   * Hemoglobin \>=80 g/L
   * Creatinine clearance \>=30 milliliter per minute (mL/min)
   * Total serum bilirubin \<=1.5\*upper limit normal (ULN), \>=2.0\*ULN for participants with Gilbert's syndrome
   * Liver transaminases (alanine aminotransferase \[ALT\]/ aspartate aminotransferase \[AST\]) Serum ALT or AST \<=3.0\*ULN (\<5\*ULN if enzyme elevations are due to MM-related diffuse hepatic infiltrations).
5. Has received the final dose of any of the following treatments/procedures within the specified minimum intervals before first dose of TAK-573:

   * Chemotherapy, including proteasome inhibitors and immunomodulatory imide drug.(IMiDs) 14 days
   * Antimyeloma antibody therapy 21 days
   * Corticosteroid therapy for myeloma 7 days
   * Radiation therapy for localized bone lesions 7 days
   * Major surgery 21 days.

Exclusion Criteria:

1. Has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia or IgM myeloma, lymphoplasmacytic lymphoma, or plasma cell leukemia.
2. Previous intolerance to combination agent.
3. For the pomalidomide expansion group only: no prior treatment with pomalidomide.
4. Inability to take prophylaxis needed for combination agent (deep vein thrombosis prophylaxis for pomalidomide, antiviral prophylaxis for proteasome inhibitor).
5. Who have received autologous stem cell transplant (SCT) within 60 days before first infusion of TAK-573 or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
6. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade \<=1 or baseline, except for sensory or motor neuropathy which should have recovered to Grade \<=2 or baseline, Grade \<2 for participants receiving bortezomib.
7. Has a chronic condition requiring the use of systemic corticosteroids \>10 milligram per day (mg/day) of prednisone or equivalent.