LINKER-MM3: A Study to Learn How Linvoseltamab (REGN5458) Will Work Compared to the Elotuzumab, Pomalidimide and Dexamethasone (EPd) Combination, in Participants With Relapsed/Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
The primary objective of this study is to compare progression-free survival (PFS) per the Independent Review Committee (IRC) between participants treated with linvoseltamab monotherapy and EPd.
The key secondary objectives are:
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To compare the anti-tumor activity per IRC between linvoseltamab monotherapy and EPd as measured by
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objective response
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≥very good partial response (VGPR)
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≥ complete response (CR)
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To compare the incidence of minimal residual disease (MRD) negative status (10^-5) in the bone marrow between linvoseltamab monotherapy and EPd
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To compare overall survival (OS) between linvoseltamab monotherapy and EPd
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To evaluate the treatment effects on pain symptom between linvoseltamab monotherapy and EPd
Other secondary objectives include:
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To evaluate the safety and tolerability of linvoseltamab monotherapy compared to EPd
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To compare PFS per the investigator between participants treated with linvoseltamab monotherapy and EPd.
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To compare the anti-tumor activity per the investigator between linvoseltamab monotherapy and EPd as measured by
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Objective response
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≥VGPR
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≥CR
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To evaluate duration of response (DOR) per investigator and IRC for participants achieving objective response on linvoseltamab monotherapy and on EPd
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To evaluate the duration of MRD negative status in the bone marrow in participants receiving linvoseltamab monotherapy and EPd
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To evaluate the time to response for participants with response ≥PR for linvoseltamab monotherapy and EPd
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To evaluate the pharmacokinetics (PK) of linvoseltamab
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To evaluate the immunogenicity of linvoseltamab
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To evaluate the effects on patient reported quality of life (QoL), functioning and symptoms between linvoseltamab monotherapy and EPd
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: REGN5458 or Linvoseltamab Randomization 1:1 |
Drug: REGN5458
REGN5458 will be administered by intravenous (IV) infusion
Other Names:
|
| Active Comparator: Elotuzumab/Pomalidomide/Dexamethasone (EPd) Randomization 1:1 |
Drug: Elotuzumab
Elotuzumab will be administered by IV infusion
Other Names:
Drug: Pomalidomide
Pomalidomide capsules will administered by mouth (PO)
Other Names:
Drug: Dexamethasone
Dexamethasone tablets/capsules will be administered PO and/or by IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) [Up to approximatively 5 years]
Secondary Outcome Measures
- Objective Response (OR) greater or equal to Partial Response (PR) per IMWG response criteria [Up to approximatively 5 years]
ORR will be assessed using IMWG response critieria by the IRC
- Objective Response Rate (ORR) greater or equal to Very Good Partial Response (VGPR) per IMWG response criteria as determined by IRC [Up to approximatively 5 years]
- Objective Response Rate (ORR) greater or equal to Complete Response (CR) per IMWG response criteria as determined by IRC [Up to approximatively 5 years]
- Incidence of minimal residual disease (MRD) negative status [Up to approximatively 5 years]
- Overall Survival (OS) [Up to approximatively 5 years]
- Mean change from baseline in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 [Baseline to week 12]
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 [Up to approximatively 5 years]
- Incidence of treatment emergent adverse events (TEAEs) [Up to approximatively 5 years]
- Severity of treatment emergent adverse events (TEAEs) [Up to approximatively 5 years]
- Incidence of adverse events of special interest (AESI) [Up to approximatively 5 years]
- Severity of adverse events of special interest (AESI) [Up to approximatively 5 years]
- Incidence of Serious Adverse Events (SAE) [Up to approximatively 5 years]
- Severity of Serious Adverse Events (SAE) [Up to approximatively 5 years]
- ORR greater or equal to PR per IMWG response criteria [Up to approximatively 5 years]
ORR will be assessed using IMWG response critieria by the investigator
- ORR greater or equal to VGPR per IMWG response criteria [Up to approximatively 5 years]
ORR will be assessed using IMWG response criteria by the investigator
- ORR greater or equal to CR per IMWG response criteria [Up to approximatively 5 years]
ORR will be assessed using IMWG response criteria by the investigator
- Duration of Response (DoR) as per IMWG response criteria [Up to approximatively 5 years]
DoR will be assessed using IMWG response criteria by the investigator and IRC
- Duration of MRD negative status in the bone marrow [Up to approximatively 5 years]
- Time from randomization to objective response (≥PR) as per IMWG response criteria [From randomization to objective response, up to approximatively 5 years]
As determined by IRC and investigator
- Concentration of linvoseltamab in the serum over time [Up to approximatively 5 years]
- Incidence of antidrug antibodies (ADAs) [Up to approximatively 5 years]
- Titer of antidrug antibodies (ADAs) [Up to approximatively 5 years]
- Incidence of neutralizing antibodies (NAbs) to linvoseltamab over time [Up to approximatively 5 years]
- Proportion of Pain Responders [At week 12]
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) [Baseline to week 12]
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]) [Baseline to week 12]
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.
- Change from baseline in Patient Global Impression of Severity (PGIS) [Baseline to week 12]
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".
- Change from baseline in Patient Global Impression of Change (PGIC) [Baseline to week 12]
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"
- Change from baseline in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) [Baseline to week 12]
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.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG 2 solely due to local symptoms of myeloma (e.g. pain) may be allowed after discussion with the Medical Monitor.
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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.
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Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
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Adequate hematologic, hepatic, renal and cardiac function, as well as evidence of adequate bone marrow reserves
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Life expectancy of at least 6 months
Key Exclusion Criteria:
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Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
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Prior treatment with elotuzumab and/or pomalidomide
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Participants with known MM brain lesions or meningeal involvement
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Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
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History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment
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Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies
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Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
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Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C; or another uncontrolled infection, as defined in the protocol.
NOTE: Other protocol defined inclusion/exclusion criteria apply
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trials Adminstrator, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R5458-ONC-2245
- 2022-501396-62-00