Clinical Trial Finder

Inclusion Criteria:

• - Have a diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria.

• - Be newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to: ineligible due to advanced age OR; ineligible due to the presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT OR; deferral of high-dose chemotherapy with ASCT as initial treatment.

• - Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.

• - A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.

• - A participant must agree not to plan to father a child while enrolled in this study or within 3 months after the last dose of study treatment.

Exclusion Criteria:

• - Received any prior therapy for multiple myeloma or smoldering myeloma other than a short course of corticosteroids (not to exceed 40 milligrams [mg] of dexamethasone, or equivalent per day for a maximum of 4 days, total of 160 mg dexamethasone or equivalent).

In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equals to (>=)20 mg of dexamethasone during the Screening Phase.

• - Had plasmapheresis within 28 days of randomization.

• - Had a stroke, transient ischemic attack, or seizure within 6 months prior to randomization.

• - Known allergies, hypersensitivity, or intolerance to teclistamab or talquetamab excipients.

• - Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.

- Myeloma Frailty Index of >=2 with the exception of participants who have a score of 2 based on age alone

Teclistamab is a full-size, immunoglobin G4 proline, alanine, alanine (IgG4-PAA) bispecific antibody that targets the cluster of differentiation 3 (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). Talquetamab is a full-size, humanized IgG4-PAA bispecific antibody designed to target the CD3 receptor complex on T cells and G protein-coupled receptor class C group 5 member D (GPRC5D), which is a 7-transmembrane receptor protein that is classified as a type C G protein-coupled receptor. DRd is an approved regimen for the treatment of participants with newly diagnosed, transplant-ineligible multiple myeloma. The primary hypothesis of this study is that Tec-DR and Tal-DR will significantly improve progression free survival (PFS) or the rate of sustained minimal residual disease (MRD)-negative complete response (CR) (greater than [>]12 months) compared with DRd in participants with newly diagnosed multiple myeloma who are ineligible or not intended for autologous stem cell transplant (ASCT) as initial therapy. The study will be conducted in 3 phases: Screening, Treatment, and Follow-up. Safety Assessment includes adverse events (AEs), laboratory test results, vital sign measurements, physical examination findings, assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade, and immune effector cell associated encephalopathy (ICE) score (Tec-DR and Tal-DR).

Arms

Experimental: Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)

Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.

Experimental: Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)

Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.

Active Comparator: Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)

Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.

Interventions

Drug: - Teclistamab

Teclistamab will be administered as SC injection.

Drug: - Daratumumab

Daratumumab will be administered as SC injection.

Drug: - Lenalidomide

Lenalidomide will be administered orally.

Drug: - Dexamethasone

Dexamethasone will be administered either orally or intravenously (IV).

Drug: - Talquetamab

Talquetamab will be administered as SC injection.