Clinical trial NCT06932562: A Study to Learn How Safe and How Well Linvoseltamab Works Compared to Standard Treatment in Adult Patients With Multiple Myeloma Who Are Not Eligible for Transplant
Official title: A Randomized, Open-Label, Controlled Phase 3 Study of Comparing Daratumumab, Lenalidomide and Dexamethasone Induction Followed by Linvoseltamab Versus Continued Daratumumab, Lenalidomide, and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma (MM)
Transplant ineligible
Newly diagnosed
Linvoseltamab
BCMA X CD3 bispecific antibody
CD38 antibody
Lenalidomide
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2025-04-17
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible).

The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.


Eligibility criteria: Inclusion Criteria:

1. Participants must have confirmed diagnosis of symptomatic MM per IMWG criteria.
2. Participants must not be considered a candidate for high-dose chemotherapy (HDT) and ASCT, as described in the protocol.
3. Participants must have measurable disease as defined in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5. Participants must have clinical laboratory values within a prespecified range.

Exclusion Criteria:

1. International Myeloma Working Group Frailty Index of 2 with the exception of participants who have a score of 2 based on age alone.
2. Participants who defer transplant due to personal preference.
3. Participants with non-secretory MM, active plasma cell leukemia, known light-chain (AL) amyloidosis in the presence of a concurrent diagnosis of myeloma, any other form of amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome.
4. Any prior therapy for monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with the exception of:

   * focal radiation and/or
   * a short course of corticosteroids as defined in the protocol.
5. Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM
6. Participants who have known central nervous system (CNS) or meningeal involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), a history of a neurocognitive condition or CNS movement disorder, OR a history of seizure, transient ischemic attack (TIA), stroke or seizure within 12 months prior to study C1D1.
7. Participants who have uncontrolled intercurrent illness.
8. Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.
9. History of allogeneic hematopoietic stem cell transplantation or solid organ transplant at any time.

NOTE Other protocol defined inclusion/exclusion criteria apply.

Primary outcomes:
measure: Minimal Residual Disease (MRD)
timeFrame: up to 11 years
measure: MRD negative CR status by BICR
timeFrame: up to 11 years
measure: Progression Free Survival (PFS) per IMWG criteria
timeFrame: up to 11 years
measure: PFS as determined by BICR
timeFrame: up to 11 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 11 years
measure: Objective Response (OR) of Complete Response (CR)
timeFrame: up to 11 years
measure: OR of Very Good Partial Response (VGPR)
timeFrame: up to 11 years
measure: OR of Partial Response (PR)
timeFrame: up to 11 years
measure: Sustained MRD
timeFrame: up to 11 years
measure: Duration of response (DOR) of stringent (s)CR
timeFrame: up to 11 years
measure: Duration of response (DOR) of CR
timeFrame: up to 11 years
measure: Duration of response (DOR) of VGPR
timeFrame: up to 11 years
measure: Duration of response (DOR) of PR
timeFrame: up to 11 years
measure: Time to response ≥CR
timeFrame: up to 11 years
measure: Time to response ≥VGPR
timeFrame: up to 11 years
measure: Time to response ≥PR
timeFrame: up to 11 years
measure: Disease progression
timeFrame: up to 11 years
measure: Incidence of TEAEs
timeFrame: up to 11 years
measure: Severity of TEAEs
timeFrame: up to 11 years
measure: Serious Adverse Events
timeFrame: up to 11 years
measure: Concentrations of linvoseltamab
timeFrame: up to 11 years
measure: Incidence antidrug antibodies
timeFrame: up to 11 years
measure: Titer of ADA
timeFrame: up to 11 years
measure: EORTC QLQ-C30 Global Health Status / Quality of Life
timeFrame: up to 11 years
measure: EORTC QLQ-C30 Physical Functioning (PF)
timeFrame: up to 11 years
measure: EORTC QLQ-C30 Role Functioning (RF)
timeFrame: up to 11 years
measure: EORTC QLQ-C30 Pain
timeFrame: up to 11 years
measure: EORTC QLQ-C30 Fatigue
timeFrame: up to 11 years
measure: EQ-5D-5L VAS
timeFrame: up to 11 years
Other outcomes:
Locations:
Study officials:
affiliation: A.O.U. Città della Salute e della Scienza di Torino
name: Roberto Mina
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Claudia Stege
role: PRINCIPAL_INVESTIGATOR
References: