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A Study to Learn How Linvoseltamab (REGN5458) Will Work Compared to the Elotuzumab, Pomalidomide and Dexamethasone (EPd) Combination, in Participants With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

Primary Purpose

Relapsed Refractory Multiple Myeloma

Status

Recruiting

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Linvoseltamab

Elotuzumab

Pomalidomide

Dexamethasone

About this trial

This is an interventional treatment trial for Relapsed Refractory Multiple Myeloma focused on measuring BCMA X CD3 Bispecific Monoclonal Antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Age 18 years or older (or legal adult age in the country) at the time of the screening visit. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG 2 solely due to local symptoms of myeloma (eg. pain) may be allowed after discussion with the Medical Monitor. Received at least 1 and no more than 4 prior lines of anti-neoplastic MM therapies, including lenalidomide and a proteasome inhibitor and demonstrated disease progression on or after the last therapy as defined by the 2016 IMWG criteria. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory, as described in the protocol. Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol Adequate hematologic, hepatic, renal and cardiac function, as well as evidence of adequate bone marrow reserves Life expectancy of at least 6 months Key Exclusion Criteria: Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). Prior treatment with elotuzumab and/or pomalidomide Participants with known MM brain lesions or meningeal involvement Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); or another uncontrolled infection, as defined in the protocol. NOTE: Other protocol defined inclusion/exclusion criteria apply

Sites / Locations

Regeneron Study SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Linvoseltamab

Elotuzumab/Pomalidomide/Dexamethasone (EPd)

Arm Description

Randomization 1:1

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC)

Secondary Outcome Measures

Objective Response (OR) greater or equal to Partial Response (PR) per IMWG response criteria as determined by the IRC

Objective Response Rate (ORR) greater or equal to Very Good Partial Response (VGPR) per IMWG response criteria as determined by IRC

Objective Response Rate (ORR) greater or equal to Complete Response (CR) per IMWG response criteria as determined by IRC

Incidence of minimal residual disease (MRD) negative status

Overall Survival (OS)

Mean change from baseline in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3

The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF Item 3 uses a numeric rating scale to assess pain severity and pain interference in the past 24 hours. The numeric rating scale ranges from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain.

Progression-free Survival (PFS) per IMWG response criteria as determined by the investigator

Incidence of treatment emergent adverse events (TEAEs)

Severity of treatment emergent adverse events (TEAEs)

Incidence of adverse events of special interest (AESI)

Severity of adverse events of special interest (AESI)

Incidence of Serious Adverse Events (SAE)

Severity of Serious Adverse Events (SAE)

ORR greater or equal to PR per IMWG response criteria as determined by the investigator

ORR greater or equal to VGPR per IMWG response criteria as determined by the investigator

ORR greater or equal to CR per IMWG response criteria as determined by the investigator

Duration of Response (DoR) as per IMWG response criteria as determined by the investigator

DoR as per IMWG response criteria as determined by the IRC

Duration of MRD negative status in the bone marrow

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator

Concentration of linvoseltamab in the serum over time

Incidence of antidrug antibodies (ADAs)

Titer of antidrug antibodies (ADAs)

Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time

Proportion of Pain Responders

Defined by at least a 2-point reduction from baseline in the BPI-SF Item 3 without an increase in analgesic use

Change from baseline in patient-reported global health status/quality of life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

Change from baseline in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20])

The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.

Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS)

The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe". The global anchor, PGIS will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.

Patient-Reported Outcomes in Patient Global Impression of Change (PGIC)

The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change". The global anchor, PGIC will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.

Change from baseline in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L])

The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.

Full Information

NCT ID

NCT05730036

First Posted

February 6, 2023

Last Updated

October 2, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05730036

Brief Title

A Study to Learn How Linvoseltamab (REGN5458) Will Work Compared to the Elotuzumab, Pomalidomide and Dexamethasone (EPd) Combination, in Participants With Relapsed/Refractory Multiple Myeloma

Acronym

LINKER-MM3

Official Title

An Open-label, Randomized, Phase 3 Study of Linvoseltamab (REGN5458; Anti- BCMA x Anti-CD3 Bispecific Antibody) Versus the Combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), in Patients With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 18, 2023 (Actual)

Primary Completion Date

December 26, 2032 (Anticipated)

Study Completion Date

December 26, 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

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study is researching an experimental drug called linvoseltamab, also called REGN5458. Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after many other therapies had failed. These participants were no longer benefiting from standard medications and had no good treatment options. In that study, some participants who were treated with linvoseltamab had improvement of their myeloma (shrinkage of their tumors), including some participants who had complete responses (that is, the treatment got rid of all evidence of myeloma in their bodies). This study is focused on participants who have multiple myeloma that has returned or needs to be treated again after one to four prior treatments and have standard cancer treatment options available to them. The aim of the study is to see how safe and effective linvoseltamab is compared to a combination of three cancer drugs: elotuzumab, pomalidomide and dexamethasone (called "EPd" in this form), one of these standard treatment options. Half of the participants in this study will get linvoseltamab, and the other half will get EPd. Both linvoseltamab and EPd will be referred to as "study drugs" in this form. The study is looking at several other research questions, including: How long participants benefit from receiving linvoseltamab compared with EPd How many participants treated with linvoseltamab or EPd have improvement of their multiple myeloma and by how much What side effects happen from taking linvoseltamab compared to EPd How long participants live while receiving treatment or after treatment with linvoseltamab compared to EPd If there is any improvement in pain after treatment with linvoseltamab compared to EPd

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed Refractory Multiple Myeloma

Keywords

BCMA X CD3 Bispecific Monoclonal Antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

286 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Linvoseltamab

Arm Type

Experimental

Arm Description

Randomization 1:1

Arm Title

Elotuzumab/Pomalidomide/Dexamethasone (EPd)

Arm Type

Active Comparator

Arm Description

Randomization 1:1

Intervention Type

Drug

Intervention Name(s)

Linvoseltamab

Other Intervention Name(s)

REGN5458

Intervention Description

REGN5458 will be administered by intravenous (IV) infusion

Intervention Type

Drug

Intervention Name(s)

Elotuzumab

Other Intervention Name(s)

Empliciti

Intervention Description

Elotuzumab will be administered by IV infusion

Intervention Type

Drug

Intervention Name(s)

Pomalidomide

Other Intervention Name(s)

Pomalyst

Intervention Description

Pomalidomide capsules will administered by mouth (PO)

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

Decadron

Intervention Description

Dexamethasone tablets/capsules will be administered PO and/or by IV infusion

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC)

Time Frame

Up to approximatively 5 years

Secondary Outcome Measure Information:

Title

Objective Response (OR) greater or equal to Partial Response (PR) per IMWG response criteria as determined by the IRC

Time Frame

Up to approximatively 5 years

Title

Objective Response Rate (ORR) greater or equal to Very Good Partial Response (VGPR) per IMWG response criteria as determined by IRC

Time Frame

Up to approximatively 5 years

Title

Objective Response Rate (ORR) greater or equal to Complete Response (CR) per IMWG response criteria as determined by IRC

Time Frame

Up to approximatively 5 years

Title

Incidence of minimal residual disease (MRD) negative status

Time Frame

Up to approximatively 5 years

Title

Overall Survival (OS)

Time Frame

Up to approximatively 5 years

Title

Mean change from baseline in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3

Description

Time Frame

Baseline to week 12

Title

Progression-free Survival (PFS) per IMWG response criteria as determined by the investigator

Time Frame

Up to approximatively 5 years

Title

Incidence of treatment emergent adverse events (TEAEs)

Time Frame

Up to approximatively 5 years

Title

Severity of treatment emergent adverse events (TEAEs)

Time Frame

Up to approximatively 5 years

Title

Incidence of adverse events of special interest (AESI)

Time Frame

Up to approximatively 5 years

Title

Severity of adverse events of special interest (AESI)

Time Frame

Up to approximatively 5 years

Title

Incidence of Serious Adverse Events (SAE)

Time Frame

Up to approximatively 5 years

Title

Severity of Serious Adverse Events (SAE)

Time Frame

Up to approximatively 5 years

Title

ORR greater or equal to PR per IMWG response criteria as determined by the investigator

Time Frame

Up to approximatively 5 years

Title

ORR greater or equal to VGPR per IMWG response criteria as determined by the investigator

Time Frame

Up to approximatively 5 years

Title

ORR greater or equal to CR per IMWG response criteria as determined by the investigator

Time Frame

Up to approximatively 5 years

Title

Duration of Response (DoR) as per IMWG response criteria as determined by the investigator

Time Frame

Up to approximatively 5 years

Title

DoR as per IMWG response criteria as determined by the IRC

Time Frame

Up to approximatively 5 years

Title

Duration of MRD negative status in the bone marrow

Time Frame

Up to approximatively 5 years

Title

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC

Time Frame

From randomization to objective response, up to approximatively 5 years

Title

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator

Time Frame

From randomization to objective response, up to approximatively 5 years

Title

Concentration of linvoseltamab in the serum over time

Time Frame

Up to approximatively 5 years

Title

Incidence of antidrug antibodies (ADAs)

Time Frame

Up to approximatively 5 years

Title

Titer of antidrug antibodies (ADAs)

Time Frame

Up to approximatively 5 years

Title

Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time

Time Frame

Up to approximatively 5 years

Title

Proportion of Pain Responders

Description

Defined by at least a 2-point reduction from baseline in the BPI-SF Item 3 without an increase in analgesic use

Time Frame

At week 12

Title

Change from baseline in patient-reported global health status/quality of life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

Description

Time Frame

Baseline to week 12

Title

Change from baseline in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20])

Description

Time Frame

Baseline to week 12

Title

Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS)

Description

Time Frame

Baseline to week 12

Title

Patient-Reported Outcomes in Patient Global Impression of Change (PGIC)

Description

Time Frame

Baseline to week 12

Title

Change from baseline in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L])

Description

Time Frame

Baseline to week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Administrator

Phone

844-734-6643

clinicaltrials@regeneron.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials Adminstrator

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Regeneron Study Site

City

Incheon

ZIP/Postal Code

28265

Country

Korea, Republic of

Individual Site Status

Recruiting

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 Study to Learn How Linvoseltamab (REGN5458) Will Work Compared to the Elotuzumab, Pomalidomide and Dexamethasone (EPd) Combination, in Participants With Relapsed/Refractory Multiple Myeloma

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