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 3RecruitingNCT06932562

European Myeloma Network B.V.1,000 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,000

Conditions

Multiple Myeloma

Interventions

LinvoseltamabDRUG

Administered per the protocol

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (59)

Flinders Medical Centre

Adelaide, Australia

RECRUITING

Box Hill Hospital

Box Hill, Australia

RECRUITING

Canberra Hospital

Canberra, Australia

RECRUITING

Barwon Health, University Hospital Geelong

Geelong, Australia

Outcomes

Primary Outcomes

Minimal Residual Disease (MRD)

Minimal Residual Disease (MRD) negative Complete Remission (CR) status at 10\^-5 per International Myeloma Working Group (IMWG) criteria

Time frame: up to 11 years

MRD negative CR status by BICR

MRD negative CR status at 10\^-5 as determined by the Blinded Independent Central Review (BICR)

Time frame: up to 11 years

Progression Free Survival (PFS) per IMWG criteria

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.

Time frame: up to 11 years

PFS as determined by BICR

Time frame: up to 11 years

Secondary Outcomes

Overall Survival (OS)

Overall Survival (OS), measured from the date of from randomization to the date the subject's death

Time frame: up to 11 years

Objective Response (OR) of Complete Response (CR)

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

Time frame: up to 11 years

OR of Very Good Partial Response (VGPR)

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

Time frame: up to 11 years

OR of Partial Response (PR)

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

Time frame: up to 11 years

Sustained MRD

Sustained MRD negative CR (sMRD) at 10\^-5 per IMWG criteria

Time frame: up to 11 years

Duration of response (DOR) of stringent (s)CR

duration of response to best overall response of stringent sCR, per IMWG response criteria

Time frame: up to 11 years

Duration of response (DOR) of CR

duration of response to best overall response of CR, per IMWG response criteria

Time frame: up to 11 years

Duration of response (DOR) of VGPR

duration of response to best overall response of VGPR, per IMWG response criteria

Time frame: up to 11 years

Duration of response (DOR) of PR

duration of response to best overall response of PR, per IMWG response criteria

Time frame: up to 11 years

Time to response ≥CR

Time from randomization to objective response (≥CR) as per IMWG response criteria

Time frame: up to 11 years

Time to response ≥VGPR

Time from randomization to objective response (≥VGPR) as per IMWG response criteria

Time frame: up to 11 years

Time to response ≥PR

Time from randomization to objective response (≥PR) as per IMWG response criteria

Time frame: up to 11 years

Disease progression

Time to disease progression per IMWG response criteria

Time frame: up to 11 years

Incidence of TEAEs

Incidence of treatment emergent adverse events (TEAEs)

Time frame: up to 11 years

Severity of TEAEs

Severity of treatment emergent adverse events (TEAEs)

Time frame: up to 11 years

Serious Adverse Events

Incidence of Serious Adverse Events (SAE)

Time frame: up to 11 years

Concentrations of linvoseltamab

Concentrations of linvoseltamab in serum over time

Time frame: up to 11 years

Incidence antidrug antibodies

Incidence of antidrug antibodies (ADAs) to linvoseltamab

Time frame: up to 11 years

Titer of ADA

Titer of ADA to linvoseltamab

Time frame: up to 11 years

EORTC QLQ-C30 Global Health Status / Quality of Life

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.

Time frame: up to 11 years

EORTC QLQ-C30 Physical Functioning (PF)

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

Time frame: up to 11 years

EORTC QLQ-C30 Role Functioning (RF)

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

Time frame: up to 11 years

EORTC QLQ-C30 Pain

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

Time frame: up to 11 years

EORTC QLQ-C30 Fatigue

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

Time frame: up to 11 years

EQ-5D-5L VAS

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

Time frame: up to 11 years

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

Overview

Conditions

Interventions

Eligibility

Locations (59)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts