LINKER-MGUS1: A Proof-of-concept Study to Learn Whether Linvoseltamab Can Prevent Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06140524

Collaborator

(none)

104

Enrollment

Arms

93.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary purpose of the study is to investigate whether early treatment with the study drug can prevent the development of multiple myeloma. This requires understanding the safety and tolerability of the study drug (how your body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells and prevents the development of multiple myeloma). All participants will start treatment with gradually increasing doses of linvoseltamab (step-up doses) before they start receiving the assigned full dose. The study is split into 2 parts.

In Part 1, separate groups of 3-6 patients will receive different full doses of linvoseltamab to evaluate the short-term side effects (safety) observed within the first 35 days after starting treatment, to make sure the study drug is well tolerated, and to help make a decision about the dosing regimens chosen for Part 2.
In Part 2, a larger number of participants will be randomized to different dosing regimens to further assess the side effects of linvoseltamab, and to evaluate the ability of linvoseltamab to treat HR-MGUS and NHR-SMM and prevent progression to multiple myeloma.

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

How many participants treated with linvoseltamab (study drug) 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 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)

Condition or Disease	Intervention/Treatment	Phase
Monoclonal Gammopathy of Undetermined Significance (MGUS) Smoldering Multiple Myeloma (SMM)	Drug: Linvoseltamab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Anticipated Study Start Date :

Apr 30, 2024

Anticipated Primary Completion Date :

Feb 26, 2032

Anticipated Study Completion Date :

Feb 26, 2032

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Safety Run-In (Part 1) Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab.	Drug: Linvoseltamab Administration by intravenous (IV) infusion Other Names: REGN5458
Experimental: Expansion (Part 2) - Dose regimen 1 Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens	Drug: Linvoseltamab Administration by intravenous (IV) infusion Other Names: REGN5458
Experimental: Expansion (Part 2) - Dose regimen 2 Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens	Drug: Linvoseltamab Administration by intravenous (IV) infusion Other Names: REGN5458
Experimental: Expansion (Part 2) - Dose regimen 3 Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens	Drug: Linvoseltamab Administration by intravenous (IV) infusion Other Names: REGN5458
Experimental: Expansion (Part 2) - Dose regimen 4 Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens	Drug: Linvoseltamab Administration by intravenous (IV) infusion Other Names: REGN5458

Outcome Measures

Primary Outcome Measures

Frequency of adverse events of special interest (AEI) during the safety observation period [35 days]
Part 1 As assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system version 5 (for all grades). AESI include grade 2 or higher cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), grade 3 or higher tumor lysis syndrome (TLS), infusion-related reaction (IRR), allergic reactions, infections and hepatitis B virus (HBV) reactivation
Frequency of treatment-emergent adverse event (TEAEs) during the safety observation period [35 days]
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs during the safety observation period [35 days]
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Achievement of complete response (CR) as determined by the investigator [Up to 5.5 years]
Part 2

Secondary Outcome Measures

Frequency of TEAEs [Up to 5.5 years]
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs [Up to 5.5 years]
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Frequency of serious adverse events (SAEs) [Up to 5.5 years]
Severity of SAEs [Up to 5.5 years]
Frequency of laboratory abnormalities [Up to 5.5 years]
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of laboratory abnormalities [Up to 5.5 years]
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Minimal residual disease (MRD) negativity among participants that achieve a response of CR [Up to 5.5 years]
Sustained MRD negativity on an annual basis [Up to 3 years after achievement of CR]
Overall response of partial response (PR) or better as determined by the investigator [Up to 5.5 years]
Duration of response (DOR) as determined by the investigator [Up to 5.5 years]
Biochemical progression-free survival (PFS) as determined by the investigator [Up to 5.5 years]
Concentration of linvoseltamab in serum over time [Up to 9 months]
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time [Up to 9 months]
Titer of ADAs to linvoseltamab over time [Up to 9 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

HR-MGUS or NHR-SMM as defined in the protocol
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Adequate hematologic and hepatic function, as described in the protocol
Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 by the modification of diet in renal disease (MDRD) equation.

Key Exclusion Criteria:

High-risk SMM according to the 20-2-20 risk stratification model (Mayo criteria), as defined in the protocol
Evidence of any of myeloma-defining events, as described in the protocol
Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic MM
Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of the first dose of linvoseltamab
Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection.