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

Monoclonal Gammopathy of Undetermined Significance (MGUS) Clinical Trial

— LINKER-MGUS1  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06140524
• Other study ID #: R5458-ONC-2257
• Secondary ID: 2023-505242-25-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 30, 2024
• Est. completion date: February 26, 2032

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy of undetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma (NHR-SMM). This requires understanding the safety and tolerability of the study drug (how the body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells). 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) and tolerability of the study drug within the first 5 weeks after starting treatment. The data collected will help to 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 eliminate abnormal plasma cells in 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: February 26, 2032
• Est. primary completion date: February 26, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 m2 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 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 NOTE: Other protocol defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Monoclonal Gammopathy of Undetermined Significance
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Paraproteinemias
• Smoldering Multiple Myeloma
• Smoldering Multiple Myeloma (SMM)

Intervention

Drug:
• Linvoseltamab
Administration by intravenous (IV) infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events of special interest (AESI) during the safety observation period	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	35 days
Primary	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)	35 days
Primary	Severity of TEAEs during the safety observation period	Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)	35 days
Primary	Achievement of complete response (CR) as determined by the investigator	Part 2	Up to 5.5 years
Secondary	Frequency of TEAEs	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 5.5 years
Secondary	Severity of TEAEs	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 5.5 years
Secondary	Frequency of serious adverse events (SAEs)		Up to 5.5 years
Secondary	Severity of SAEs		Up to 5.5 years
Secondary	Frequency of laboratory abnormalities	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 5.5 years
Secondary	Severity of laboratory abnormalities	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 5.5 years
Secondary	Minimal residual disease (MRD) negativity among participants that achieve a response of CR		Up to 5.5 years
Secondary	Sustained MRD negativity on an annual basis		Up to 3 years after achievement of CR
Secondary	Overall response of partial response (PR) or better as determined by the investigator		Up to 5.5 years
Secondary	Duration of response (DOR) as determined by the investigator		Up to 5.5 years
Secondary	Biochemical progression-free survival (PFS) as determined by the investigator		Up to 5.5 years
Secondary	Concentration of linvoseltamab in serum over time		Up to 9 months
Secondary	Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time		Up to 9 months
Secondary	Titer of ADAs to linvoseltamab over time		Up to 9 months