Clinical trial NCT05828511: A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Official title: Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Newly diagnosed multiple myeloma (NDMM)
Autologous stem cell transplantation (ASCT)
Cluster of differentiation 3 (CD3)
BCMA
High dose chemotherapy (HDT)
International Myeloma Working Group (IMWG)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.
Primary purpose: TREATMENT

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

The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM.

This study consists of 2 phases:

* In Phase 1, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2.
* In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM.

The study is looking at several research questions, including:

* What side effects may happen from taking linvoseltamab?
* What the right dosing regimen is for linvoseltamab?
* How many participants treated with linvoseltamab have improvement of their disease and for how long?
* The effects of linvoseltamab study treatment before and after transplant
* How much linvoseltamab is in the blood at different times?
* Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects).


Eligibility criteria: Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
2. Confirmed diagnosis of symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria
3. Measurable disease, according to the 2016 IMWG response criteria, as defined in the protocol
4. No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
5. Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
6. Participants must be age \<70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.

Key Exclusion Criteria:

1. Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
2. Known central nervous system (CNS) involvement with MM, known or suspected progressive multifocal leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
3. Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
4. Diagnosis of non-secretory MM, active plasma cell leukemia, primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: End of the Observation period; up to day 28
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Severity of TEAEs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Severity of AESIs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
timeFrame: Up to 5 years
measure: Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
timeFrame: Up to 5 years
measure: Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
timeFrame: Up to 5 years
measure: Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
timeFrame: Up to 5 years
measure: Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II
timeFrame: Up to 5 years
Secondary outcomes:
measure: Concentrations of Linvoseltamab in serum
timeFrame: Post-Last Linvoseltamab Dose, up to 12 weeks
measure: Concentrations of total soluble B-cell maturation antigen (BCMA)
timeFrame: Post-Last Linvoseltamab Dose, up to 12 weeks
measure: Incidence of anti-drug antibodies (ADAs) to Linvoseltamab
timeFrame: Post-Last Linvoseltamab Dose, up to 30 days
measure: Titer of ADAs to Linvoseltamab
timeFrame: Post-Last Linvoseltamab Dose, up to 30 days
measure: Objective response rate (ORR) measured using the IMWG criteria
timeFrame: Up to 5 years
measure: Duration of Response (DOR) measured using the IMWG criteria
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Progression-free survival (PFS) measured using the IMWG criteria
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Incidence of TEAEs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Severity of TEAEs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Incidence of AESIs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Severity of AESIs
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
timeFrame: Up to 5 years
measure: MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Time to response (TTR) as measured using the IMWG criteria
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: ORR by risk levels
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: MRD-negative rstatus by risk levels
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: DOR by risk levels
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: TTR by risk levels
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: PFS by risk levels
timeFrame: Post-Last Linvoseltamab Dose, up to 90 days
measure: Incidence of MRD-negative status
timeFrame: Up to 5 years
measure: Cluster of differentiation 34+ (CD34+) stem cell yield
timeFrame: At cycle 4 of induction (each cycle is 28 days long)
measure: Time to neutrophil engraftment
timeFrame: Up to 100 days post-transplant
measure: Time to platelet engraftment
timeFrame: Up to 100 days post-transplant
measure: PFS after ASCT followed by 3 cycles of linvoseltamab
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute/SCRI
state: Colorado
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Villejuif
country: France
facility: Gustave Roussy
state: Ile De France
city: Paris
country: France
facility: Hopital Necker
state: Ile-de-France
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire (CHU) de Poitiers
state: Nouvelle-Aquitaine
city: Lille
country: France
facility: CHU De Lille
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire (CHU) Montpellier
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Pitié Salpetriere APHP
city: Oviedo
country: Spain
facility: Hospital Universitario Central De Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario Doctor Balmis Alicante
state: Comunidad Valenciana
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Salud Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Institut Catala dOncologia (ICO Hospitalet)
city: Madrid
country: Spain
facility: Universitary Hospital La Princesa
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: La Fe University Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: