An Open-Label, Randomized Phase 3 Study of Linvoseltamab Monotherapy and Linvoseltamab Plus Carfilzomib Versus Standard of Care Combination Regimens in Patients With Relapsed/Refractory Multiple Myeloma

Official 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)

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 915 participants

Study Arms

• Part 1: Arm A (EXPERIMENTAL)
• Part 1: Arm B (EXPERIMENTAL)
• Part 2: Arm A (EXPERIMENTAL)
• Part 2: Arm B (EXPERIMENTAL)
• Part 2: Arm C (EXPERIMENTAL)

Interventions

• DRUG: Linvoseltamab — Administered per the protocol
• DRUG: Carfilzomib — Administered per the protocol
• DRUG: Daratumumab — Administered per the protocol
• DRUG: Dexamethasone — Administered per the protocol
• DRUG: Pomalidomide — Administered per the protocol

Primary Outcomes

• Occurrence of Treatment Emergent Adverse Events (TEAEs) (Up to 5 years)
• Severity of TEAEs (Up to 5 years)
• Occurrence of Adverse Events of Special Interest (AESI) (Up to 5 years)
• Severity of AESIs (Up to 5 years)
• Occurrence of Serious Adverse Events (SAEs) (Up to 5 years)

Secondary Outcomes

• Occurrence of grade ≥2 Cytokine Release Syndrome (CRS) (Up to 28 days)
• Timing of grade ≥2 CRS (Up to 28 days)
• Overall Survival (OS) (Up to 7 years)
• Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC (Up to 5 years)
• Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC (Up to 5 years)

Eligibility Criteria

Key Inclusion Criteria:

1. 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
2. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
3. Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy

Key Exclusion Criteria:

1. 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
2. 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)
3. Known Central Nervous System (CNS) involvement of myeloma including meningeal involvement
4. History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy (PML), or CNS movement disorder

NOTE: Other protocol defined inclusion/exclusion criteria apply

Trial Locations

• Memorial Sloan Kettering Cancer Center, New York, New York, United States
• OhioHealth, Columbus, Ohio, United States
• Mater Misericordiae Ltd, Brisbane, Queensland, Australia
• Gold Coast Hospital and Health Service, Southport, Queensland, Australia
• Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, South Korea
• Seoul National University Hospital, Seoul, South Korea
• Severance Hospital; Division of Hematology, Seoul, South Korea
• Samsung Medical Center, Seoul, South Korea
• Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
• Ulsan University Hospital, Ulsan, South Korea
• ...and 6 more locations

Contact Information

• Clinical Trials Administrator — CONTACT
  Phone: 844-734-6643
  Email: clinicaltrials@regeneron.com

Study Officials

• Clinical Trial Management — STUDY_DIRECTOR
  Regeneron Pharmaceuticals

More Relapsed and/or Refractory Multiple Myeloma (RRMM) Trials

View all Relapsed and/or Refractory Multiple Myeloma (RRMM) clinical trials