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Testing REGN5458 for patients with relapsed or refractory multiple myeloma

Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

Phase1; Phase2 Interventional Regeneron Pharmaceuticals · NCT03761108

This study is testing a new drug called REGN5458 to see if it can safely help adults with relapsed or refractory multiple myeloma who have few treatment options.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment387 (estimated)
Ages18 Years and up
SexAll
SponsorRegeneron Pharmaceuticals Industry-sponsored
Drugs / interventionslinvoseltamab, CAR-T
Locations40 sites (Miami, Florida and 39 other locations)
Trial IDNCT03761108 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and optimal dosing of REGN5458 in adult patients diagnosed with relapsed or refractory multiple myeloma. It will assess side effects, how the drug functions in the body, and its potential effectiveness in treating cancer. The study includes a dose escalation phase to determine the best therapeutic approach for patients who have limited treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults with active multiple myeloma who have exhausted standard treatment options.

Not a fit: Patients with early-stage multiple myeloma or those who have not yet undergone multiple lines of therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat multiple myeloma.

How similar studies have performed: Other studies have shown promise with similar approaches in treating multiple myeloma, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
2. Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
3. Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.

   * Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:

     a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
   * Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:

     a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.
   * Phase 2 (Cohorts 1 and 2):

   Patients with MM whose disease meets the following criteria:

   a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory\* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
   * Phase 2 (Cohort 3):

   Patients with MM whose disease meets the following criteria:
   1. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
   2. Patients must be triple- refractory, defined as being refractory\* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

      * Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or \<25% response to therapy.

   AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:

   • Treatment with a CAR-T must have been associated with a response of PR or better, and

   • If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with linvoseltamab.

   Key Exclusion Criteria:

1\. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Patients with known MM brain lesions or meningeal involvement 3. Cardiac ejection fraction \<40% by echocardiogram or multi-gated acquisition scan (MUGA) 4. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excluded and BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.

5\. History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment

Note: Other protocol defined inclusion / exclusion criteria apply

Where this trial is running

Miami, Florida and 39 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Multiple MyelomaRelapsed, Refractory
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.