A Study to Compare Linvoseltamab Monotherapy and Linvoseltamab + Carfilzomib Combination Therapy With Standard-of-Care Combination Regimens in Adult Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
- Conditions
- Relapsed and/or Refractory Multiple Myeloma (RRMM)
- Interventions
- Registration Number
- NCT07222761
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching a drug called linvoseltamab (also called "study drug") either given alone or in combination with another anti-myeloma drug called carfilzomib, compared to several standard treatments for progressive Multiple Myeloma (MM) after at least 1 but no more than 3 prior therapies.
The aim of this study is to see if the safety and efficacy of linvoseltamab alone or in combination with carfilzomib can deliver better outcomes (deeper and longer responses that help extend life) than standard treatment options.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 915
- Participant with RRMM who received at least 1 but not more than 3 prior lines of therapy, which must have included treatment with lenalidomide and either a Protease Inhibitor (PI) or anti-CD38 monoclonal antibody
- Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
- Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy
Key
- Prior treatment with a T cell-based immunotherapy targeting BCMA, including BCMA-directed bispecific antibodies, Bispecific T-cell Engagers (BiTEs), and Chimeric Antigen Receptor (CAR) T cells. Antibody-drug conjugates targeting BCMA (eg, belantamab mafodotin) are not excluded
- Diagnosis of plasma cell leukemia, symptomatic amyloidosis (including myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Known Central Nervous System (CNS) involvement of myeloma including meningeal involvement
- History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy (PML), or CNS movement disorder
NOTE: Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Arm A Linvoseltamab - Part 1: Arm B Linvoseltamab - Part 2: Arm C Pomalidomide - Part 1: Arm B Carfilzomib - Part 2: Arm A Linvoseltamab - Part 2: Arm B Linvoseltamab - Part 2: Arm B Carfilzomib - Part 2: Arm C Carfilzomib - Part 2: Arm C Daratumumab - Part 2: Arm C Dexamethasone - Part 2: Arm C Bortezomib -
- Primary Outcome Measures
Name Time Method Occurrence of Treatment Emergent Adverse Events (TEAEs) Up to 5 years Part 1
Severity of SAEs Up to 5 years Part 1
Progression-Free Survival (PFS) per IMWG response criteria as determined by BIRC Up to 5 years Part 2
Severity of TEAEs Up to 5 years Part 1
Severity of AESIs Up to 5 years Part 1
Occurrence of Adverse Events of Special Interest (AESI) Up to 5 years Part 1
Occurrence of Serious Adverse Events (SAEs) Up to 5 years Part 1
Minimal Residual Disease (MRD)-negative Complete Response (CR) At 12 months Part 2
- Secondary Outcome Measures
Name Time Method MRD-negative CR criteria at any time Up to 5 years Part 2
Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC Up to 5 years Part 2
Occurrence of grade ≥2 Cytokine Release Syndrome (CRS) Up to 28 days Part 1
Timing of grade ≥2 CRS Up to 28 days Part 1
Overall Survival (OS) Up to 7 years Part 2
Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC Up to 5 years Part 2
Achievement of CR or better per IMWG response criteria as determined by BIRC Up to 5 years Part 2
Duration Of Response (DOR) as per IMWG response criteria Up to 5 years Part 2
Time To Progression (TTP) as per IMWG response criteria Up to 5 years Part 2
Time To Next Treatment (TTNT) Up to 5 years Part 2
Second PFS Up to 5 years Part 2
Time to PR IMWG response category Up to 5 years Part 2
Time to VGPR IMWG response category Up to 5 years Part 2
Time to CR IMWG response category Up to 5 years Part 2
Time to stringent Complete Response (sCR) IMWG response category Up to 5 years Part 2
Sustained MRD-negative CR Up to 5 years Part 2
Duration of MRD-negative CR Up to 5 years Part 2
Occurrence of TEAEs Up to 5 years Part 2
Severity of TEAEs Up to 5 years Part 2
Occurrence of AESIs Up to 5 years Part 2
Severity of AESIs Up to 5 years Part 2
Occurrence of SAEs Up to 5 years Part 2
Severity of SAEs Up to 5 years Part 2
Concentrations of linvoseltamab in serum over time Up to 5 years Part 2
Incidence of Antidrug Antibodies (ADAs) to linvoseltamab Up to 5 years Part 2
Magnitude of ADAs to linvoseltamab Up to 5 years Part 2
Concentrations total soluble B-cell Maturation Antigen (sBCMA) in serum over time Up to 5 years Part 2
Change from baseline in Global Health Status (GHS)/Quality of Life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Up to 5 years Part 2 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer.
Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."Change from baseline in Physical Functioning (PF), per EORTC QLQ-C30 Up to 5 years Part 2
Change from baseline in Role Functioning (RF), per EORTC QLQ-C30 Up to 5 years Part 2
Change from baseline in pain, per EORTC QLQ-C30 Up to 5 years Part 2
Change from baseline in fatigue, per EORTC QLQ-C30 Up to 5 years Part 2
Change in patient reported Disease Symptoms (DS) per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) Up to 5 years Part 2 EORTC QLQ-MY20 is an accompanying 20-item validated questionnaire that measure quality of life among patients living with MM across 4 scales (disease symptoms, side effect of treatment, body image and future perspective). A high score represents a high level of symptoms or problems.
Change in patient reported Treatment Side Effects (TSE) per EORTC QLQ-MY20 Up to 5 years Part 2
Change in patient-reported health state per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) Visual Analogue Scale (VAS) Up to 5 years Part 2 The EQ-5D-5L is a generic questionnaire that measures HRQoL across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (no problems, slight problems, some problems, severe problems and extreme problems) and a VAS of pain (where 0: no pain and 10: worst pain), higher scores indicate higher pain.
Change in patient-reported overall impact of treatment per Functional Assessment of Chronic Illness Therapy (FACIT) item GP5 Up to 5 years Part 2 FACIT Item GP5 is a recommended item by the Federal Drug Administration (FDA) in its recent draft guidance for cancer trials to assess patient-reported overall impact of treatment toxicity. It uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much)