A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Phase 2RecruitingNCT06140524

Regeneron Pharmaceuticals116 enrolled

Overview

This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM). The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of HR-MGUS and NHR-SMM. The study is looking at several other research questions, including: * How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-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 the drug less effective or could lead to side effects).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

116

Conditions

Monoclonal Gammopathy of Undetermined Significance (MGUS)Smoldering Multiple Myeloma (SMM)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. HR-MGUS or NHR-SMM as defined 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 (GFR) ≥30 mL/min/1.73 m\^2 by the Modification of Diet in Renal Disease (MDRD) equation Key Exclusion Criteria: 1. High-risk SMM, as defined in the protocol 2. Evidence of any of myeloma-defining events, as described in the protocol 3. Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM 4. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol 5. Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 28 days of the first dose of linvoseltamab 6. 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 NOTE: Other protocol defined inclusion/exclusion criteria apply

Locations (13)

Johns Hopkins Hospital

Baltimore, Maryland, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

RECRUITING

University of Michigan Health

Ann Arbor, Michigan, United States

RECRUITING

Stony Brook University Hospital

Stony Brook, New York, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

RECRUITING

University of Washington

Seattle, Washington, United States

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, Spain

RECRUITING

Hospital Universitari Mutua Terrassa

Terrassa, Barcelona, Spain

RECRUITING

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Murcia, Spain

RECRUITING

Hospital de Cabuenes

Gijón, Principality of Asturias, Spain

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

Frequency of Adverse Events Interest (AEI) during the safety observation period

Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules

Time frame: 35 days

Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period

Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: 35 days

Severity of TEAEs during the safety observation period

Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: 35 days

Achievement of Complete Response (CR) as determined by the investigator

Part 2

Time frame: Up to 5.5 years

Secondary Outcomes

Frequency of TEAEs

As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: Up to 5.5 years

Severity of TEAEs

As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: Up to 5.5 years

Frequency of Serious Adverse Events (SAEs)

Time frame: Up to 5.5 years

Severity of SAEs

Time frame: Up to 5.5 years

Frequency of laboratory abnormalities

As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: Up to 5.5 years

Severity of laboratory abnormalities

As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Time frame: Up to 5.5 years

Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR

Time frame: Up to 5.5 years

Sustained MRD negativity on an annual basis

Time frame: Up to 3 years after achievement of CR

Overall response of Partial Response (PR) or better as determined by the investigator

Time frame: Up to 5.5 years

Duration Of Response (DOR) as determined by the investigator

Time frame: Up to 5.5 years

Biochemical Progression-Free Survival (PFS) as determined by the investigator

Time frame: Up to 5.5 years

Concentration of linvoseltamab in serum over time

Time frame: Up to 9 months

Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration

Time frame: Up to 5.5. years

Magnitude of ADAs to linvoseltamab over the study duration

Time frame: Up to 5.5. years

A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts