A Randomized, Open-Label, Controlled Phase 3 Study of Comparing Daratumumab, Lenalidomide and Dexamethasone Induction Followed by Linvoseltamab Versus Continued Daratumumab, Lenalidomide, and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients

Official Summary

This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible). The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,000 participants

Study Arms

• Control arm DRd (ACTIVE_COMPARATOR)
• Experimental Arm DRd+ linvolsetamab (EXPERIMENTAL)

Interventions

• DRUG: Linvoseltamab — Administered per the protocol
• DRUG: Daratumumab — Administered per the protocol
• DRUG: Lenalidomide — Administered per the protocol
• DRUG: Dexamethasone — Administered per the protocol

Primary Outcomes

• Minimal Residual Disease (MRD) (up to 11 years)
• MRD negative CR status by BICR (up to 11 years)
• Progression Free Survival (PFS) per IMWG criteria (up to 11 years)
• PFS as determined by BICR (up to 11 years)

Secondary Outcomes

• Overall Survival (OS) (up to 11 years)
• Objective Response (OR) of Complete Response (CR) (up to 11 years)
• OR of Very Good Partial Response (VGPR) (up to 11 years)
• OR of Partial Response (PR) (up to 11 years)
• Sustained MRD (up to 11 years)

Eligibility Criteria

Inclusion Criteria:

1. Participants must have confirmed diagnosis of symptomatic MM per IMWG criteria.
2. Participants must not be considered a candidate for high-dose chemotherapy (HDT) and ASCT, as described in the protocol.
3. Participants must have measurable disease as defined in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5. Participants must have clinical laboratory values within a prespecified range.

Exclusion Criteria:

1. International Myeloma Working Group Frailty Index of 2 with the exception of participants who have a score of 2 based on age alone.
2. Participants who defer transplant due to personal preference.
3. Participants with non-secretory MM, active plasma cell leukemia, known light-chain (AL) amyloidosis in the presence of a concurrent diagnosis of myeloma, any other form of amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome.
4. Any prior therapy for monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with the exception of:

   * focal radiation and/or
   * a short course of corticosteroids as defined in the protocol.
5. Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM
6. Participants who have known central nervous system (CNS) or meningeal involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), a history of a neurocognitive condition or CNS movement disorder, OR a history of seizure, transient ischemic attack (TIA), stroke or seizure within 12 months prior to study C1D1.
7. Participants who have uncontrolled intercurrent illness.
8. Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.
9. History of allogeneic hematopoietic stem cell transplantation or solid organ transplant at any time.

NOTE Other protocol defined inclusion/exclusion criteria apply.

Trial Locations

• Flinders Medical Centre, Adelaide, Australia
• Box Hill Hospital, Box Hill, Australia
• Canberra Hospital, Canberra, Australia
• Barwon Health, University Hospital Geelong, Geelong, Australia
• Austin Hospital, Heidelberg, Australia
• Nepean Cancer Centre, Kingswood, Australia
• Northern Hospital, Melbourne, Australia
• Sunshine Coast Health, Sunshine Coast, Australia
• Ordensklinikum Linz, Linz, Austria
• Klinik Ottakring, Vienna, Austria
• ...and 10 more locations

Contact Information

• Silvia Villa — CONTACT
  Phone: +31 10 268 70 65
  Email: silvia.villa@emn.org

Study Officials

• Roberto Mina — PRINCIPAL_INVESTIGATOR
  A.O.U. Città della Salute e della Scienza di Torino
• Claudia Stege — PRINCIPAL_INVESTIGATOR
  Erasmus Medical Center

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