Back to resultsA 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
Primary Purpose
Smoldering Multiple Myeloma (SMM)
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Linvoseltamab
Sponsored by
About this trial
This is an interventional treatment trial for Smoldering Multiple Myeloma (SMM) focused on measuring Linvoseltamab, Multiple Myeloma (MM), B cell maturation antigen (BCMA), Bispecific antibody
Eligibility Criteria
KEY Inclusion Criteria: High-risk SMM diagnosis within 5 years of study enrollment Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate hematologic and hepatic function, as described in the protocol Estimated glomerular filtration rate ≥30 mL/min/1.73 m^2 KEY Exclusion Criteria: 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) Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma 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 first dose of study drug Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Safety Run-In (Part 1)
Expansion (Part 2)
Arm Description
Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab.
Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.
Outcomes
Primary Outcome Measures
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)
Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period
Severity of TEAEs during the safety run-in observation period
Complete response (CR) as determined by the investigator
Minimal residual disease (MRD) negativity
MRD negativity
Secondary Outcome Measures
Frequency of TEAEs during expansion part
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs during expansion part
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Frequency of serious adverse events (SAEs)
Severity of SAEs
Frequency of laboratory abnormalities
Severity of laboratory abnormalities
Overall response of partial response (PR) or better
Duration of response (DOR)
Biochemical progression-free-survival (PFS)
MRD negativity among participants that achieve very good partial response (VGPR) or better
Sustained MRD negativity
Time from treatment initiation to date of any myeloma-defining event
Time from start of treatment to date of progression to MM or death
Time to initiation of first-line treatment for MM
Overall survival (OS)
Concentration of linvoseltamab in serum over time
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Titer of ADAs to linvoseltamab over time
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05955508
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
April 30, 2032 (Anticipated)
Study Completion Date
April 30, 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoldering Multiple Myeloma (SMM)
Keywords
Linvoseltamab, Multiple Myeloma (MM), B cell maturation antigen (BCMA), Bispecific antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Safety Run-In (Part 1)
Arm Type
Experimental
Arm Description
Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab.
Arm Title
Expansion (Part 2)
Arm Type
Experimental
Arm Description
Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.
Intervention Type
Drug
Intervention Name(s)
Linvoseltamab
Other Intervention Name(s)
REGN5458
Intervention Description
Administration by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Frequency of adverse events of special interest (AESI) during the safety run-in observation period
Description
AESI include grade 2 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
Time Frame
Up to 35 days
Title
Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period
Time Frame
Up to 35 days
Title
Severity of TEAEs during the safety run-in observation period
Time Frame
Up to 35 days
Title
Complete response (CR) as determined by the investigator
Time Frame
Up to 7 years
Title
Minimal residual disease (MRD) negativity
Time Frame
At 12 months
Title
MRD negativity
Time Frame
At 24 months
Secondary Outcome Measure Information:
Title
Frequency of TEAEs during expansion part
Description
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Time Frame
Up to 7 years
Title
Severity of TEAEs during expansion part
Description
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Time Frame
Up to 7 years
Title
Frequency of serious adverse events (SAEs)
Time Frame
Up to 7 years
Title
Severity of SAEs
Time Frame
Up to 7 years
Title
Frequency of laboratory abnormalities
Time Frame
Up to 7 years
Title
Severity of laboratory abnormalities
Time Frame
Up to 7 years
Title
Overall response of partial response (PR) or better
Time Frame
Up to 7 years
Title
Duration of response (DOR)
Time Frame
Up to 7 years
Title
Biochemical progression-free-survival (PFS)
Time Frame
Up to 7 years
Title
MRD negativity among participants that achieve very good partial response (VGPR) or better
Time Frame
Up to 3 years after end of treatment
Title
Sustained MRD negativity
Time Frame
Up to 3 years after end of treatment
Title
Time from treatment initiation to date of any myeloma-defining event
Time Frame
Up to 7 years
Title
Time from start of treatment to date of progression to MM or death
Time Frame
Up to 7 years
Title
Time to initiation of first-line treatment for MM
Time Frame
Up to 7 years
Title
Overall survival (OS)
Time Frame
Up to 7 years
Title
Concentration of linvoseltamab in serum over time
Time Frame
Up to 2 years
Title
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Time Frame
Up to 2 years
Title
Titer of ADAs to linvoseltamab over time
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
KEY Inclusion Criteria:
High-risk SMM diagnosis within 5 years of study enrollment
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Adequate hematologic and hepatic function, as described in the protocol
Estimated glomerular filtration rate ≥30 mL/min/1.73 m^2
KEY Exclusion Criteria:
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)
Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
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 first dose of study drug
Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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 URL
https://vivli.org/
Learn more about this trial
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
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