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

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.

Interventions

• Drug Linvoseltamab
  Administered per the protocol
• Drug Daratumumab
  Administered per the protocol
• Drug Lenalidomide
  Administered per the protocol
• Drug Dexamethasone
  Administered per the protocol

Primary outcome measures

• Minimal Residual Disease (MRD) [Time frame: up to 11 years]
• MRD negative CR status by BICR [Time frame: up to 11 years]
• Progression Free Survival (PFS) per IMWG criteria [Time frame: up to 11 years]
• PFS as determined by BICR [Time frame: up to 11 years]

Secondary outcome measures (12)

• Overall Survival (OS) [Time frame: up to 11 years]
• Objective Response (OR) of Complete Response (CR) [Time frame: up to 11 years]
• OR of Very Good Partial Response (VGPR) [Time frame: up to 11 years]
• OR of Partial Response (PR) [Time frame: up to 11 years]
• Sustained MRD [Time frame: up to 11 years]
• Duration of response (DOR) of stringent (s)CR [Time frame: up to 11 years]
• Duration of response (DOR) of CR [Time frame: up to 11 years]
• Duration of response (DOR) of VGPR [Time frame: up to 11 years]
• Duration of response (DOR) of PR [Time frame: up to 11 years]
• Time to response ≥CR [Time frame: up to 11 years]
• Time to response ≥VGPR [Time frame: up to 11 years]
• Time to response ≥PR [Time frame: up to 11 years]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• International Myeloma Working Group Frailty Index of 2 with the exception of participants who have a score of 2 based on age alone.
• Participants who defer transplant due to personal preference.
• 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.
• 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.
• Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM
• 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.
• Participants who have uncontrolled intercurrent illness.
• Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.
• History of allogeneic hematopoietic stem cell transplantation or solid organ transplant at any time.

NOTE Other protocol defined inclusion/exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 11 centers

• AOU Ospedali Riuniti di Ancona — Ancona
• Azienda Ospedaliera Santa Croce e Carle - Ematologia — Cuneo
• A.O.U. Careggi — Florence
• IRCCS Ospedale Policlinico San Martino — Genova
• Ospedale di Legnano, ASST Ovest Milanese — Legnano
• Meldola-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) — Meldola
• ASST Grande Ospedale Metropolitano Niguarda — Milan
• Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda - Oncologia — Milan
• … and 3 more centers

Australia · 8 centers

• Flinders Medical Centre — Adelaide
• Box Hill Hospital — Box Hill
• Canberra Hospital — Canberra
• Barwon Health, University Hospital Geelong — Geelong
• Austin Hospital — Heidelberg
• Nepean Cancer Centre — Kingswood
• Northern Hospital — Melbourne
• Sunshine Coast Health — Sunshine Coast

Spain · 5 centers

• Institut Catala D'oncologia (Badalona) — Badalona
• Hospital Clinic De Barcelona - Myeloma and Amyloidosis Unit — Barcelona
• Hospital Quirón Salud Madrid — Madrid
• Hospital Universitario Marques De Valdecilla -Hematology and Hemotherapy Service — Santander
• Hospital Universitario la Fe, Valencia — Valencia

Czechia · 4 centers

• Fakultni Nemocnice Hradec Kralove — Hradec Králové
• University Hospital Olomouc — Olomouc
• Fakultni Nemocnice Ostrava — Ostrava
• Fakultni Nemocnice Plzen — Pilsen

Greece · 4 centers

• University Hospital of Alexandroupolis — Alexandroupoli
• Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens — Athens
• Evaggelismos Hospital — Athens
• Theagenion Cancer Hospital — Thessaloniki

Turkey (Türkiye) · 4 centers

• Ankara University Faculty of Medicine, Department of Hematology — Ankara
• Liv Hospital Ankara — Ankara
• Ege Universitesi Tip Fakultesi - Hematology — Izmir
• Ege University Medicine Faculty, Izmir — Izmir

Germany · 3 centers

• Universitaetsmedizin Greifswald — Greifswald
• Universitaetsklinikum Schleswig-Holstein -Campus Luebeck - Klinik fuer Haematologie und On — Lübeck
• University Hospital of Würzburg — Würzburg

Ireland · 3 centers

• Cork University Hospital — Cork
• Beaumont Hospital — Dublin
• University Hospital Limerick - Department of Haematology — Limerick

Norway · 3 centers

• Stavanger University Hospital — Stavanger
• St. Olavs hospital HF — Trondheim
• Vestfold Hospital Trust — Tønsberg

Austria · 2 centers

• Ordensklinikum Linz — Linz
• Klinik Ottakring — Vienna

Estonia · 2 centers

• North Estonia Medical Centre Foundation — Tallinn
• Tartu University Hospital — Tartu

Finland · 2 centers

• Helsinki University Hospital Comprehensive Cancer Center — Helsinki
• Kuopio University Hospital — Kuopio

Portugal · 2 centers

• CHUC — Coimbra
• Hospital da Luz Lisboa — Lisbon

Switzerland · 2 centers

• Universitaetsspital Basel - Zentrum fur Hamato-Onkologie — Basel
• Kantonsspital St. Gallen — Sankt Gallen

Croatia · 1 center

• University Hospital Centre Zagreb - Clinic for Internal Medicine — Zagreb

Denmark · 1 center

• Aarhus Universitetshospital — Aarhus

Netherlands · 1 center

• Erasmus MC — Rotterdam

Sweden · 1 center

• Skåne University Hospital, Region Skåne — Lund

Identifiers

NCT: NCT06932562 · EMN39 · 2024-519827-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗