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A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05730036
Recruitment Status : Recruiting
First Posted : February 15, 2023
Last Update Posted : February 20, 2024
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

This 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 this 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 participants who have returned after having received prior treatment that included lenalidomide, a proteosome inhibitor, and (for participants in some countries) a differentiation 38 (CD38) antibody. Half of the participants in this study will get linvoseltamab, and the other half will get EPd.

This 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

Condition or disease Intervention/treatment Phase
Relapsed Refractory Multiple Myeloma (RRMM) Drug: Linvoseltamab Drug: Elotuzumab Drug: Pomalidomide Drug: Dexamethasone Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 18, 2023
Estimated Primary Completion Date : December 26, 2032
Estimated Study Completion Date : December 26, 2032


Arm Intervention/treatment
Experimental: Linvoseltamab
Randomization 1:1
Drug: Linvoseltamab
REGN5458 will be administered by intravenous (IV) infusion
Other Name: REGN5458

Active Comparator: Elotuzumab/Pomalidomide/Dexamethasone (EPd)
Randomization 1:1
Drug: Elotuzumab
Elotuzumab will be administered by IV infusion
Other Name: Empliciti

Drug: Pomalidomide
Pomalidomide capsules will administered by mouth (PO)
Other Name: Pomalyst

Drug: Dexamethasone
Dexamethasone tablets/capsules will be administered PO and/or by IV infusion
Other Name: Decadron




Primary Outcome Measures :
  1. Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 exposed participants [ Time Frame: Up to approximatively 5 years ]

Secondary Outcome Measures :
  1. PFS per IMWG response criteria determined by IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  2. Objective Response (OR) of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 exposed participants [ Time Frame: Up to approximatively 5 years ]
  3. OR of PR or better per IMWG response criteria as determined by the IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  4. OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 exposed participants [ Time Frame: Up to approximatively 5 years ]
  5. OR of VGPR or better per IMWG response criteria as determined by IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  6. OR of Complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 exposed participants [ Time Frame: Up to approximatively 5 years ]
  7. OR of CR or better per IMWG response criteria as determined by IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  8. Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  9. Incidence of MRD negative status in all participants [ Time Frame: Up to approximatively 5 years ]
  10. Overall Survival (OS) in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  11. OS in all participants [ Time Frame: Up to approximatively 5 years ]
  12. Mean change in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 in participants previously exposed to CD38 [ Time Frame: 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.

  13. Mean change in the worst pain score measured by BPI-SF Item 3 in all participants [ Time Frame: 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.

  14. Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  15. Incidence TEAEs in all participants [ Time Frame: Up to approximatively 5 years ]
  16. Severity of TEAEs in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  17. Severity of TEAEs in all participants [ Time Frame: Up to approximatively 5 years ]
  18. Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  19. Incidence of AESI in all participants [ Time Frame: Up to approximatively 5 years ]
  20. Severity of AESI in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  21. Severity AESI in all participants [ Time Frame: Up to approximatively 5 years ]
  22. Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  23. Incidence of SAE in all participants [ Time Frame: Up to approximatively 5 years ]
  24. Severity of SAE in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  25. Severity of SAE in all participants [ Time Frame: Up to approximatively 5 years ]
  26. PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  27. PFS per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  28. OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  29. OR of PR or better per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  30. OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  31. OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  32. OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  33. OR of CR or better per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  34. Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  35. DoR as per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  36. DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  37. DoR as per IMWG response criteria as determined by the IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  38. Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  39. Duration of MRD negative status in the bone marrow in all participants [ Time Frame: Up to approximatively 5 years ]
  40. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  41. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in all participants [ Time Frame: Up to approximatively 5 years ]
  42. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  43. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in all participants [ Time Frame: Up to approximatively 5 years ]
  44. Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  45. Concentration of linvoseltamab in the serum over time in all participants [ Time Frame: Up to approximatively 5 years ]
  46. Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  47. Incidence of ADAs in all participants [ Time Frame: Up to approximatively 5 years ]
  48. Titer of ADAs in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  49. Titer of ADAs in all participants [ Time Frame: Up to approximatively 5 years ]
  50. Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 [ Time Frame: Up to approximatively 5 years ]
  51. Incidence of Nabs to linvoseltamab over time in all participants [ Time Frame: Up to approximatively 5 years ]
  52. Proportion of Pain Responders in participants previously exposed to CD38 [ Time Frame: 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 using the modified Analgesic Quantification Algorithm (AQA).

  53. Proportion of Pain Responders in all participants [ Time Frame: 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 using the modified Analgesic Quantification Algorithm (AQA).

  54. Change 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) in participants previously exposed to CD38 [ Time Frame: 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."

  55. Change in patient-reported QoL, per EORTC QLQ-C30 in all participants [ Time Frame: 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."

  56. Change in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) in participants previously exposed to CD38 [ Time Frame: 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.

  57. Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants [ Time Frame: 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.

  58. Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 [ Time Frame: 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".

    The global anchor, PGIS will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.


  59. Patient-Reported Outcomes in PGIS in all participants [ Time Frame: 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".

    The global anchor, PGIS will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.


  60. Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 [ Time Frame: 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".

    The global anchor, PGIC will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.


  61. Patient-Reported Outcomes in PGIC in all participants [ Time Frame: 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".

    The global anchor, PGIC will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.


  62. Change in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) in participants previously exposed to CD38 [ Time Frame: 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.

  63. Change in patient-reported general health status per EQ-5D-5L in all participants [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Age 18 years or older (or legal adult age in the country) at the time of the screening visit.
  2. 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.
  3. 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.

    Note: Participants in Israel also must have previously received a CD38 antibody. Participants in the EU and the UK must have previously received 2 to 4 prior lines of therapy, including a CD38 antibody.

  4. Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
  5. Adequate hematologic, hepatic, renal and cardiac function, as well as evidence of adequate bone marrow reserves
  6. Life expectancy of at least 6 months

Key Exclusion Criteria:

  1. Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  2. Prior treatment with elotuzumab and/or pomalidomide
  3. Participants with known MM brain lesions or meningeal involvement
  4. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
  5. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment. Participants who have received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Steroids at doses equivalent to suppletion doses may be acceptable.
  6. Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Note: BCMA antibody-drug conjugates are allowed.
  7. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
  8. 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05730036


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
Show Show 37 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05730036    
Other Study ID Numbers: R5458-ONC-2245
2022-501396-62-00 ( Other Identifier: EUCT Number )
First Posted: February 15, 2023    Key Record Dates
Last Update Posted: February 20, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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.
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
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
BCMA X CD3 Bispecific Monoclonal Antibody
CD38 antibody
Proteasome inhibitor
Lenalidomide
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Pomalidomide
Elotuzumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors