• Overall Response Rate (ORR) [ Time Frame: Up to Month 36 ]
  ORR based on International Myeloma Working Group (IMWG) Uniform Response Criteria, is defined as the percentage of participants who achieved a PR or better during the study. PR is defined as greater than or equal to (>=) 50 percent (%) reduction of serum M-protein, and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligram per 24 hours (mg/24 h). If serum and urine M protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels is required in place of M protein criteria.
• Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to Month 36) ]
• Number of Participants With Grade 3 or Higher TEAEs [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to Month 36) ]
  Adverse event (AE) Grades will be evaluated as per NCI CTCAE, version 4.03.
• Number of Participants with TEAEs Leading to Treatment Discontinuation [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to Month 36) ]
• Number of Participants With AEs Leading to On-study Deaths [ Time Frame: From screening up to 30 days after the last dose of study drug (up to Month 36) ]

The drug being tested in this study is called TAK-079. TAK-079 is being tested to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) when added to 1 of 2 standard backbone regimens (LenDex or VRd) with newly diagnosed NDMM for whom stem cell transplantation (SCT) is not planned as initial therapy.

The study will enroll approximately 36 participants. Participants will be non-randomly assigned to one of the two treatment groups:

• TAK-079 and LenDex
• TAK-079 and VRd

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 36 months. Participants will have a follow-up visit 30 days after the last dose of study drug or before the start of subsequent alternative anticancer therapy, to permit the detection of any delayed AEs.

• Drug: TAK-079
  TAK-079 subcutaneously.
• Drug: Lenalidomide
  Lenalidomide orally.
• Drug: Dexamethasone
  Dexamethasone orally.
• Drug: Bortezomib
  Bortezomib subcutaneously.

• Experimental: TAK-079 and LenDex
  TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to Month 36. The dosage of dexamethasone can be reduced for participants who are greater than (>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.
  Interventions:

  • Drug: TAK-079
  • Drug: Lenalidomide
  • Drug: Dexamethasone
• Experimental: TAK-079 and VRd
  TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to Month 36. The dosage of dexamethasone can be reduced for participants who are >75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.
  Interventions:

  • Drug: TAK-079
  • Drug: Lenalidomide
  • Drug: Dexamethasone
  • Drug: Bortezomib

Inclusion Criteria:

1. Must have previously untreated multiple myeloma (MM) as defined by the IMWG criteria requiring treatment according to the investigator.
2. Are appropriate candidates for either the VRd or Rd backbone antimyeloma therapy according to the investigator.

3. Must have measurable disease defined by at least 1 of the following:

   • Serum M-protein >=1 gram per deciliter (g/dL) (>=10 gram/liter [g/L]).
   • Urine M-protein >=200 mg/24 h.
   • Serum FLC assay: involved FLC level >=10 mg/dL (≥100 milligram per liter [mg/L]) provided the serum FLC ratio is abnormal.
4. Participants receiving lenalidomide must be able to take concurrent prophylactic anticoagulation per standard clinical practice as directed by the investigator.
5. Life expectancy >3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (<=) 2.

Exclusion Criteria:

1. Prior systemic therapy for MM.

   o treatment with bisphosphonates or a single course of glucocorticoids does not disqualify the participant (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg [for example, 40 milligram per day (mg/d) for 4 days] of dexamethasone).

2. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device) within 4 weeks of the first dose of TAK-079 or any agent in the backbone regimen and throughout the duration of this trial.

3. Prior radiation therapy within 14 days of the first dose of TAK-079 or any backbone regimen agents.

   NOTE: Prophylactic localized ("spot") radiation for areas of pain is allowed.

4. Major surgery within 4 weeks before Cycle 1 Day 1 (kyphoplasty is not considered major surgery). Participants should be fully recovered from any surgically related complications.
5. Plasmapheresis within 28 days of randomization.
6. If plasmacytoma is the only measurable parameter for assessing disease response, participant is not eligible because of difficult response evaluation.
7. Clinical signs of meningeal involvement of MM exhibited during screening.
8. Serum positive for human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
9. Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the TAK-079 formulation or agents in the backbone regimen (lenalidomide, bortezomib, dexamethasone) as per the respective prescribing information or for TAK-079, as outlined in the current investigator's brochure (IB).
10. Systemic infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of TAK-079 or any agent in the backbone regimen. Urinary tract infection is not considered a systemic infection.
11. A 12-lead electrocardiogram (ECG) showing a QT interval corrected by Frederica's formula (QTcF) >470 milliseconds. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG.
12. Diagnosis of primary amyloidosis, Waldenstrom's disease, monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) per IMWG criteria or standard diagnostic criteria, plasma cell leukemia (according to the World Health Organization [WHO] criterion: >=20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 *10^9/L), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS syndrome), myelodysplastic syndrome, or myeloproliferative syndrome.
13. History of myelodysplastic syndrome or another malignancy other than MM, except for the following: any malignancy that has been in complete remission for 2 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer (Gleason score <=6 without known metastatic disease and with no requirement for therapy, or requiring only hormonal therapy and stable prostate-specific antigen for >=1 year before initiation of study therapy), breast carcinoma in situ with full surgical resection, and treated medullary or papillary thyroid cancer.