Back to resultsA Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment. (LINKER-MM4)
Primary Purpose
Multiple Myeloma
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Linvoseltamab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Newly diagnosed multiple myeloma (NDMM), Autologous stem cell transplantation (ASCT), Cluster of differentiation 3 (CD3), BCMA, High dose chemotherapy (HDT), International Myeloma Working Group (IMWG)
Eligibility Criteria
Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Confirmed diagnosis of symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria Measurable disease, according to the 2016 IMWG response criteria, as defined in the protocol No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance. Key Exclusion Criteria: Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis Known central nervous system (CNS) involvement with MM, as well as known neurocognitive conditions, CNS movement disorder, or history of seizure within 12 months prior to study enrollment Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy Diagnosis of non-secretory MM, active plasma cell leukemia, primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) Note: Other protocol-defined Inclusion/Exclusion criteria apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1 cohort
Phase 2 - transplant ineligible cohort
Phase 2 - transplant eligible cohort
Arm Description
Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve.
Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol.
Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol
Outcomes
Primary Outcome Measures
Incidence of dose-limiting toxicities (DLTs)
Phase 1
Incidence of treatment-emergent adverse events (TEAEs)
Phase 1
Severity of treatment-emergent adverse events (TEAEs)
Phase 1
Incidence of adverse events of special interest (AESIs)
Phase 1
Severity of adverse events of special interest (AESIs)
Phase 1
Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
Phase 2
Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
Phase 2 Transplant-eligible cohort
Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
Phase 2 Transplant-eligible cohort
Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
Phase 2 Transplant-ineligible cohort
Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II
Phase 2 Transplant ineligible cohort
Secondary Outcome Measures
Concentrations of Linvoseltamab in serum
Phases 1 and 2
Concentrations of total soluble B-cell maturation antigen (BCMA)
Phases 1 and 2
Incidence of anti-drug antibodies (ADAs) to Linvoseltamab
Phases 1 and 2
Titer of ADAs to Linvoseltamab
Phases 1 and 2
Objective response rate (ORR) measured using the IMWG criteria
Phase 1
Duration of Response (DOR) measured using the IMWG criteria
Phase 1
Progression-free survival (PFS) measured using the IMWG criteria
Phase 1
Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
Phase 1
Incidence of treatment-emergent adverse events (TEAEs)
Phase 2
Severity of TEAEs
Phase 2
Incidence of adverse events of special interest (AESIs)
Phase 2
Severity of AESIs
Phase 2
ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Phase 2
MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Phase 2
DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Phase 2
PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Phase 2
Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Phase 2
Time to response (TTR) as measured using the IMWG criteria
Phase 2
ORR by risk levels
Phase 2
MRD-negative rstatus by risk levels
Phase 2
DOR by risk levels
Phase 2
TTR by risk levels
Phase 2
PFS by risk levels
Phase 2
Incidence of MRD-negative status
Phase 2
Cluster of differentiation 34+ (CD34+) stem cell yield
Phase 2 Transplant-eligible cohort
Time to neutrophil engraftment
Phase 2 Transplant-eligible cohort
Time to platelet engraftment
Phase 2 Transplant-eligible cohort
PFS after ASCT followed by 3 cycles of linvoseltamab
Phase 2 Transplant-eligible cohort
Full Information
NCT ID
NCT05828511
First Posted
April 12, 2023
Last Updated
August 17, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05828511
Brief Title
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment.
Acronym
LINKER-MM4
Official Title
Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 27, 2023 (Anticipated)
Primary Completion Date
September 30, 2035 (Anticipated)
Study Completion Date
September 30, 2035 (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
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of the study are:
For Phase 1
To find out if linvoseltamab is safe and well tolerated
To find out what the most appropriate dosing schedule would be for future clinical trials
For Phase 2
•To find out if it works to treat multiple myeloma
The secondary objectives of the study are:
For Phase 1 and 2
To find out how linvoseltamab moves throughout the body over time (pharmacokinetics)
To find out how much B-cell maturation antigen (BCMA) participants have in their blood
To find out if the participants' immune systems respond to linvoseltamab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Newly diagnosed multiple myeloma (NDMM), Autologous stem cell transplantation (ASCT), Cluster of differentiation 3 (CD3), BCMA, High dose chemotherapy (HDT), International Myeloma Working Group (IMWG)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 cohort
Arm Type
Experimental
Arm Description
Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve.
Arm Title
Phase 2 - transplant ineligible cohort
Arm Type
Experimental
Arm Description
Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol.
Arm Title
Phase 2 - transplant eligible cohort
Arm Type
Experimental
Arm Description
Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol
Intervention Type
Drug
Intervention Name(s)
Linvoseltamab
Other Intervention Name(s)
REGN5458
Intervention Description
Linvoseltamab will be administered by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities (DLTs)
Description
Phase 1
Time Frame
End of the Observation period; up to day 28
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Severity of treatment-emergent adverse events (TEAEs)
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Incidence of adverse events of special interest (AESIs)
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Severity of adverse events of special interest (AESIs)
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
Description
Phase 2
Time Frame
Up to 5 years
Title
Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
Description
Phase 2 Transplant-eligible cohort
Time Frame
Up to 5 years
Title
Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
Description
Phase 2 Transplant-eligible cohort
Time Frame
Up to 5 years
Title
Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
Description
Phase 2 Transplant-ineligible cohort
Time Frame
Up to 5 years
Title
Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II
Description
Phase 2 Transplant ineligible cohort
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Concentrations of Linvoseltamab in serum
Description
Phases 1 and 2
Time Frame
Post-Last Linvoseltamab Dose, up to 12 weeks
Title
Concentrations of total soluble B-cell maturation antigen (BCMA)
Description
Phases 1 and 2
Time Frame
Post-Last Linvoseltamab Dose, up to 12 weeks
Title
Incidence of anti-drug antibodies (ADAs) to Linvoseltamab
Description
Phases 1 and 2
Time Frame
Post-Last Linvoseltamab Dose, up to 30 days
Title
Titer of ADAs to Linvoseltamab
Description
Phases 1 and 2
Time Frame
Post-Last Linvoseltamab Dose, up to 30 days
Title
Objective response rate (ORR) measured using the IMWG criteria
Description
Phase 1
Time Frame
Up to 5 years
Title
Duration of Response (DOR) measured using the IMWG criteria
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Progression-free survival (PFS) measured using the IMWG criteria
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
Description
Phase 1
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Severity of TEAEs
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Incidence of adverse events of special interest (AESIs)
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Severity of AESIs
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Description
Phase 2
Time Frame
Up to 5 years
Title
MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Time to response (TTR) as measured using the IMWG criteria
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
ORR by risk levels
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
MRD-negative rstatus by risk levels
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
DOR by risk levels
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
TTR by risk levels
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
PFS by risk levels
Description
Phase 2
Time Frame
Post-Last Linvoseltamab Dose, up to 90 days
Title
Incidence of MRD-negative status
Description
Phase 2
Time Frame
Up to 5 years
Title
Cluster of differentiation 34+ (CD34+) stem cell yield
Description
Phase 2 Transplant-eligible cohort
Time Frame
At cycle 4 of induction (each cycle is 28 days long)
Title
Time to neutrophil engraftment
Description
Phase 2 Transplant-eligible cohort
Time Frame
Up to 100 days post-transplant
Title
Time to platelet engraftment
Description
Phase 2 Transplant-eligible cohort
Time Frame
Up to 100 days post-transplant
Title
PFS after ASCT followed by 3 cycles of linvoseltamab
Description
Phase 2 Transplant-eligible cohort
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Confirmed diagnosis of symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria
Measurable disease, according to the 2016 IMWG response criteria, as defined in the protocol
No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.
Key Exclusion Criteria:
Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
Known central nervous system (CNS) involvement with MM, as well as known neurocognitive conditions, CNS movement disorder, or history of seizure within 12 months prior to study enrollment
Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
Diagnosis of non-secretory MM, active plasma cell leukemia, primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
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 the study 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 Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment.
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