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

Phase 3

Not yet recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Daratumumab; Drug: Linvoseltamab; Drug: Lenalidomide; Drug: Dexamethasone

• Registration Number: NCT06932562
• Lead Sponsor: European Myeloma Network B.V.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-10
• Study First Submitted QC: 2025-04-10
• Study First Posted: 2025-04-17
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-23
• Study Start: 2025-09
• Primary Completion: 2036-12
• Study Completion: 2036-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1000

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm DRd	Daratumumab	-
Control arm DRd	Lenalidomide	-
Control arm DRd	Dexamethasone	-
Experimental Arm DRd+ linvolsetamab	Linvoseltamab	-
Experimental Arm DRd+ linvolsetamab	Daratumumab	-
Experimental Arm DRd+ linvolsetamab	Lenalidomide	-
Experimental Arm DRd+ linvolsetamab	Dexamethasone	-

Primary Outcome Measures

Name	Time	Method
Minimal Residual Disease (MRD)	up to 11 years	Minimal Residual Disease (MRD) negative Complete Remission (CR) status at 10\^-5 per International Myeloma Working Group (IMWG) criteria
MRD negative CR status by BICR	up to 11 years	MRD negative CR status at 10\^-5 as determined by the Blinded Independent Central Review (BICR)
Progression Free Survival (PFS) per IMWG criteria	up to 11 years	defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per IMWG criteria.
PFS as determined by BICR	up to 11 years	defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per by BICR.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	up to 11 years	Overall Survival (OS), measured from the date of from randomization to the date the subject's death
OR of Very Good Partial Response (VGPR)	up to 11 years	To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for VGPR or better
OR of Partial Response (PR)	up to 11 years	To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for PR or better
Objective Response (OR) of Complete Response (CR)	up to 11 years	To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for Complete Response (CR) or better
Sustained MRD	up to 11 years	Sustained MRD negative CR (sMRD) at 10\^-5 per IMWG criteria
Duration of response (DOR) of stringent (s)CR	up to 11 years	duration of response to best overall response of stringent sCR, per IMWG response criteria
Duration of response (DOR) of CR	up to 11 years	duration of response to best overall response of CR, per IMWG response criteria
Duration of response (DOR) of VGPR	up to 11 years	duration of response to best overall response of VGPR, per IMWG response criteria
Duration of response (DOR) of PR	up to 11 years	duration of response to best overall response of PR, per IMWG response criteria
Time to response ≥CR	up to 11 years	Time from randomization to objective response (≥CR) as per IMWG response criteria
Time to response ≥VGPR	up to 11 years	Time from randomization to objective response (≥VGPR) as per IMWG response criteria
Time to response ≥PR	up to 11 years	Time from randomization to objective response (≥PR) as per IMWG response criteria
Disease progression	up to 11 years	Time to disease progression per IMWG response criteria
Incidence of TEAEs	up to 11 years	Incidence of treatment emergent adverse events (TEAEs)
Severity of TEAEs	up to 11 years	Severity of treatment emergent adverse events (TEAEs)
Serious Adverse Events	up to 11 years	Incidence of Serious Adverse Events (SAE)
Concentrations of linvoseltamab	up to 11 years	Concentrations of linvoseltamab in serum over time
Incidence antidrug antibodies	up to 11 years	Incidence of antidrug antibodies (ADAs) to linvoseltamab
Titer of ADA	up to 11 years	Titer of ADA to linvoseltamab
EORTC QLQ-C30 Global Health Status / Quality of Life	up to 11 years	Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported quality of life using one global health status/quality of life (GHS/QoL) scale, 5 functioning scales (physical, role, emotional, cognitive, and social) ranging from from 1 = "very poor" to 7 = "excellent" and 9 symptom scales/items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer, ranging from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
EORTC QLQ-C30 Physical Functioning (PF)	up to 11 years	Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire functioning scale Physical Functioning (PF). PF scale consist of 5 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher ("better") level of functioning
EORTC QLQ-C30 Role Functioning (RF)	up to 11 years	Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire functioning scale Role Functioning (RF). RF scale consist of 2 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher ("better") level of functioning
EORTC QLQ-C30 Pain	up to 11 years	Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire symptom scale Pain. Pain scale consist of 2 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden
EORTC QLQ-C30 Fatigue	up to 11 years	Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire symptom scale Fatigue. Fatigue scale consist of 3 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden
EQ-5D-5L VAS	up to 11 years	Change in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS).; The EQ-5D-5L is a generic questionnaire that measures Health-Related Quality of Life (HRQoL) across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (1= no problems, 2= slight problems, 3= some problems, 4= severe problems and 5= extreme problems), higher scores indicate lower health states And a visual analogue scale (VAS). VAS scale ranging from 0 = "worst" to 100 = "best" higher score indicate higher health status