A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma

Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma

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 the 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 further 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 the blood at different times?
• Whether the body makes antibodies against the study drug (which could make linvoseltamab less effective or could lead to side effects)

Study Overview

• Status: Active, not recruiting
• Conditions: Smoldering Multiple Myeloma (SMM)
• Intervention / Treatment: Drug: Linvoseltamab

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08908
    • Institut Catala D'oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra - Madrid
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon (HGUGM) - Instituto de Investigacion Sanitaria Gregorio Maranon
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Valencia, Spain, 46026
    • La Fe University Hospital
  • Valencia, Spain, 46017
    • University Hospital Doctor Peset
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Hospital Clinico Universitario Santiago de Compostela
  • Andalusia
    • Granada, Andalusia, Spain, 18014
      • Hospital Universitario Virgen De Las Nieves
  • Balearic Islands
    • Palma Mallorca, Balearic Islands, Spain, 07198
      • Hospital Universitari Son LLàtzer
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias I Pujol
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quiron Salud Madrid
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clinico Universitario Virgen de La Arrixaca
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona
  • Principality of Asturias
    • Gijón, Principality of Asturias, Spain, 33203
      • University Hospital of Cabuenes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. High-risk SMM diagnosis within 5 years of study enrollment, as described in the protocol
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 intravenous 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, as described in the protocol
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In (Part 1)	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™
Experimental: Expansion (Part 2)	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of TEAEs during the safety run-in observation period		Up to 35 days
MRD negativity		At 24 months
Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period	AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)	Up to 35 days
Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period		Up to 35 days
Complete Response (CR) as determined by the investigator		Up to 7 years
Minimal Residual Disease (MRD) negativity		At 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to 7 years
Frequency of TEAEs during expansion part	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 7 years
Severity of TEAEs during expansion part	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 7 years
Severity of SAEs		Up to 7 years
Frequency of laboratory abnormalities		Up to 7 years
Severity of laboratory abnormalities		Up to 7 years
Sustained MRD negativity		Up to 3 years after end of treatment
Time from treatment initiation to date of any myeloma-defining event		Up to 7 years
Time from start of treatment to date of progression to MM or death		Up to 7 years
Time to initiation of first-line treatment for MM		Up to 7 years
Frequency of Serious Adverse Events (SAEs)		Up to 7 years
Overall response of Partial Response (PR) or better		Up to 7 years
Duration Of Response (DOR)		Up to 7 years
Biochemical Progression-Free-Survival (PFS)		Up to 7 years
MRD negativity among participants that achieve Very Good Partial Response (VGPR) or better		Up to 3 years after end of treatment
Concentration of linvoseltamab in serum		Up to 2 years
Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab		Up to 2 years
Magnitude of ADAs to linvoseltamab		Up to 2 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): January 25, 2033
• Study Completion (Estimated): January 25, 2033

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Bispecific antibody; Multiple Myeloma (MM); Linvoseltamab; B cell Maturation Antigen (BCMA)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Precancerous Conditions; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hypergammaglobulinemia; Hemic and Lymphatic Diseases; Smoldering Multiple Myeloma; Multiple Myeloma
• Other Study ID Numbers: R5458-ONC-2256; 2023-503524-11-00 (Ctis: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes