Title
Frontline T-cell engager vs Autologous Stem cell Transplant and measurable residual disease (MRD)-guided sequential intensification thERapy in multiple myeloma (FASTER)

Description
This is an open-label, multi-site, Phase II randomized trial with response-adaptive design for newly diagnosed multiple myeloma (NDMM) participants who had prior induction therapy with one proteasome inhibitor, lenalidomide, and an anti-CD38 Monoclonal antibody (mAb) for 16-24 weeks and obtained at least partial response (PR). Eligible participants will be randomized in equal allocation to receive either elranatamab and daratumumab as consolidation and maintenance treatment (Arm A) or to undergo autologous stem cell transplant (ASCT) followed by lenalidomide and daratumumab maintenance treatment (Arm B). Patients who have residual detectable disease by MRD assessment after one year of consolidation and maintenance will undergo "late intensification" and receive the alternative therapy. Patients who achieve sustained "MRD-negativity" on 2 consecutive assessments will discontinue treatment with observation for disease progression or MRD resurgence. Elranatamab is a humanized bispecific antibody which binds to BCMA on MM cells and CD3 on T cells. Elranatamab activates and directs T cells to induce a cytotoxic T-cell response against myeloma cells. Daratumumab is a CD-38 directed therapy.

Objective
Primary Objective: To compare the depth of response obtained with elranatamab + daratumumab employed as post-induction consolidation/maintenance vs ASCT followed by lenalidomide + daratumumab.

Secondary Objectives:
To compare the sustainability of deep response obtained with elranatamab + daratumumab employed as post-induction consolidation/maintenance vs ASCT followed by lenalidomide + daratumumab.
To compare efficacy of elranatamab + daratumumab vs ASCT with lenalidomide + daratumumab as a strategy to obtain and maintain MRD negativity without the need for rescue therapy.
To describe toxicity of elranatamab + daratumumab vs ASCT with lenalidomide + daratumumab when employed as post-induction consolidation/maintenance.
To compare impact of elranatamab + daratumumab vs ASCT with lenalidomide + daratumumab on QoL and Patient-Reported Outcomes (PROs) when employed as post-induction consolidation/maintenance.
To describe effects of elranatamab + daratumumab as rescue Late Intensification therapy for participants who remain MRD-positive after ASCT and lenalidomide + daratumumab maintenance.
To describe effect of ASCT followed by lenalidomide + dartumumab as rescue Late Intensification therapy for participants who remain MRD-positive after elranatamab + daratumumab consolidation/maintenance.

Treatment This is an open-label, multi-site, Phase II randomized trial with response-adaptive design for newly diagnosed multiple myeloma (NDMM) participants who have had prior induction therapy. The primary objective of this study is to compare the rates of achieving undetectable measurable residual disease (MRD) in the bone marrow with elranatamab and daratumumab employed as post-induction consolidation and maintenance treatment (Arm A) versus autologous stem cell transplant (ASCT) followed by lenalidomide and daratumumab treatment (Arm B).

Key Eligibility For full study eligibility see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital