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

Phase 3RecruitingNCT05730036

Regeneron Pharmaceuticals410 enrolled

Overview

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 cluster of 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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 function and hepatic function within 7 days of randomization, as well as adequate renal and cardiac function and corrected calcium 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. History of progressive multifocal leukoencephalopathy (PML), known or suspected PML, or history of a neurocognitive condition or central nervous system (CNS) movement disorder (Parkinson's disease or Parkinsonism). 8. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug 9. 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 10 Cardiac ejection fraction \<40%. NOTE: Other protocol defined inclusion/exclusion criteria apply

Locations (158)

University of California Los Angeles (UCLA)

Los Angeles, California, United States

ACTIVE_NOT_RECRUITING

University of Florida Division of Sponsored Programs

Gainesville, Florida, United States

WITHDRAWN

University of Kentucky, Markey Cancer Center Clinical Research Organization

Lexington, Kentucky, United States

ACTIVE_NOT_RECRUITING

Norton Cancer Institute

Louisville, Kentucky, United States

Outcomes

Primary Outcomes

Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants

Time frame: Up to approximatively 5 years

Secondary Outcomes

PFS per IMWG response criteria determined by IRC in all participants

Time frame: Up to approximatively 5 years

Objective Response (OR) of Complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants

Time frame: Up to approximatively 5 years

OR of CR or better per IMWG response criteria as determined by IRC in all participants

Time frame: Up to approximatively 5 years

Overall Survival (OS) in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

OS in all participants

Time frame: Up to approximatively 5 years

Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence of MRD negative status in all participants

Time frame: Up to approximatively 5 years

Mean change in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 in participants previously exposed to CD38 antibodies

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.

Time frame: Baseline to week 12

Mean change in the worst pain score measured by BPI-SF Item 3 in all participants

Time frame: Baseline to week 12

Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence TEAEs in all participants

Time frame: Up to approximatively 5 years

Severity of TEAEs in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Severity of TEAEs in all participants

Time frame: Up to approximatively 5 years

Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence of AESI in all participants

Time frame: Up to approximatively 5 years

Severity of AESI in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Severity AESI in all participants

Time frame: Up to approximatively 5 years

Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence of SAE in all participants

Time frame: Up to approximatively 5 years

Severity of SAE in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Severity of SAE in all participants

Time frame: Up to approximatively 5 years

PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

PFS per IMWG response criteria as determined by the investigator in all participants

Time frame: Up to approximatively 5 years

OR of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 antibody exposed participants

Time frame: Up to approximatively 5 years

OR of PR or better per IMWG response criteria as determined by the IRC in all participants

Time frame: Up to approximatively 5 years

OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants

Time frame: Up to approximatively 5 years

OR of VGPR or better per IMWG response criteria as determined by IRC in all participants

Time frame: Up to approximatively 5 years

OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

OR of PR or better per IMWG response criteria as determined by the investigator in all participants

Time frame: Up to approximatively 5 years

OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants

Time frame: Up to approximatively 5 years

OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

OR of CR or better per IMWG response criteria as determined by the investigator in all participants

Time frame: Up to approximatively 5 years

Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

DoR as per IMWG response criteria as determined by the investigator in all participants

Time frame: Up to approximatively 5 years

DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

DoR as per IMWG response criteria as determined by the IRC in all participants

Time frame: Up to approximatively 5 years

Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Duration of MRD negative status in the bone marrow in all participants

Time frame: Up to approximatively 5 years

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

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

Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

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

Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Concentration of linvoseltamab in the serum over time in all participants

Time frame: Up to approximatively 5 years

Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence of ADAs in all participants

Time frame: Up to approximatively 5 years

Titer of ADAs in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Titer of ADAs in all participants

Time frame: Up to approximatively 5 years

Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 antibodies

Time frame: Up to approximatively 5 years

Incidence of Nabs to linvoseltamab over time in all participants

Time frame: Up to approximatively 5 years

Proportion of Pain Responders in participants previously exposed to CD38 antibodies

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).

Time frame: At week 12

Proportion of Pain Responders in all participants

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).

Time frame: At week 12

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 antibodies

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."

Time frame: Baseline to week 12

Change in patient-reported QoL, per EORTC QLQ-C30 in all participants

Time frame: Baseline to week 12

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 antibodies

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.

Time frame: Baseline to week 12

Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants

Time frame: Baseline to week 12

Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 antibodies

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.

Time frame: Baseline to week 12

Patient-Reported Outcomes in PGIS in all participants

Time frame: Baseline to week 12

Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 antibodies

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.

Time frame: Baseline to week 12

Patient-Reported Outcomes in PGIC in all participants

Time frame: Baseline to week 12

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

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.

Time frame: Baseline to week 12

Change in patient-reported general health status per EQ-5D-5L in all participants

Time frame: Baseline to week 12

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

Overview

Conditions

Interventions

Eligibility

Locations (158)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts