Clinical trial NCT05955508: A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma
Official title: Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Smoldering Multiple Myeloma (SMM)
Keywords: Linvoseltamab
Multiple Myeloma (MM)
B cell maturation antigen (BCMA)
Bispecific antibody
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-07-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing multiple myeloma (MM), a group commonly labeled as high-risk smoldering multiple myeloma (HR-SMM).

The aim of the study is to understand the safety and tolerability (how your body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study.

* In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable.
* In Part 2, linvoseltamab will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM.

The study is looking at several other research questions, including:

* How many participants treated with linvoseltamab (study drug) have improvement of their HR-SMM?
* What side effects may happen from taking the study drug?
* How much study drug is in your blood at different times?
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)


Eligibility criteria: KEY Inclusion Criteria:

1. High-risk SMM diagnosis within 5 years of study enrollment
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
3. Adequate hematologic and hepatic function, as described in the protocol
4. Estimated glomerular filtration rate ≥30 mL/min/1.73 m\^2

KEY Exclusion Criteria:

1. Evidence of myeloma defining events \*SLiM CRAB, as described in the protocol

   \*SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of ≥100 with the involved free light chain (FLC) being ≥100 mg/L, MRI with \>1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions)
2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
3. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
4. Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first dose of study drug
5. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection
6. History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient

NOTE: Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Frequency of adverse events of special interest (AESI) during the safety run-in observation period
timeFrame: Up to 35 days
measure: Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period
timeFrame: Up to 35 days
measure: Severity of TEAEs during the safety run-in observation period
timeFrame: Up to 35 days
measure: Complete response (CR) as determined by the investigator
timeFrame: Up to 7 years
measure: Minimal residual disease (MRD) negativity
timeFrame: At 12 months
measure: MRD negativity
timeFrame: At 24 months
Secondary outcomes:
measure: Frequency of TEAEs during expansion part
timeFrame: Up to 7 years
measure: Severity of TEAEs during expansion part
timeFrame: Up to 7 years
measure: Frequency of serious adverse events (SAEs)
timeFrame: Up to 7 years
measure: Severity of SAEs
timeFrame: Up to 7 years
measure: Frequency of laboratory abnormalities
timeFrame: Up to 7 years
measure: Severity of laboratory abnormalities
timeFrame: Up to 7 years
measure: Overall response of partial response (PR) or better
timeFrame: Up to 7 years
measure: Duration of response (DOR)
timeFrame: Up to 7 years
measure: Biochemical progression-free-survival (PFS)
timeFrame: Up to 7 years
measure: MRD negativity among participants that achieve very good partial response (VGPR) or better
timeFrame: Up to 3 years after end of treatment
measure: Sustained MRD negativity
timeFrame: Up to 3 years after end of treatment
measure: Time from treatment initiation to date of any myeloma-defining event
timeFrame: Up to 7 years
measure: Time from start of treatment to date of progression to MM or death
timeFrame: Up to 7 years
measure: Time to initiation of first-line treatment for MM
timeFrame: Up to 7 years
measure: Overall survival (OS)
timeFrame: Up to 7 years
measure: Concentration of linvoseltamab in serum over time
timeFrame: Up to 2 years
measure: Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
timeFrame: Up to 2 years
measure: Titer of ADAs to linvoseltamab over time
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
state: A Coruna
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
state: Andalusia
city: Gijon
country: Spain
facility: University Hospital of Cabuenes
state: Asturias
city: Palma Mallorca
country: Spain
facility: Hospital Universitari Son Llatzer
state: Baleares
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Salud Madrid
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen De La Arrixaca
state: Murcia
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 d'Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: University Hospital Doctor Peset
city: Valencia
country: Spain
facility: La Fe University Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: