First in Human (FIH) Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma


The primary objectives of the study are: Phase 1: To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended Phase 2 dose regimen (RP2DR) of REGN5458 as monotherapy in patients with relapsed or refractory Multiple Myeloma (MM) who have exhausted therapeutic options Phase 2: To assess the preliminary anti-tumor activity of REGN5458 The secondary objectives of the study are: - To evaluate the pharmacokinetic (PK) properties of REGN5458 - To characterize the immunogenicity of REGN5458 - To assess the preliminary anti-tumor activity of REGN5458 (Phase 1) - To evaluate the safety and tolerability of REGN5458 (Phase 2) - To evaluate the correlation between the activity of REGN5458 and PK (Phase 2)

SparkCures ID 1016
Trial Phase Phase 1/2
Enrollment 200 Patients
Trial Sponsors
  • Regeneron Pharmaceuticals
NCT Identifier


Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Key Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
  • Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria.
  • Phase 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:
    1. 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
    2. 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. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
    3. Phase 2: 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.
  • Adequate hematologic and hepatic function as defined in protocol
  • Serum creatinine clearance by Cockcroft-Gault >30 mL/min

Key Exclusion Criteria:

  • Diagnosis of plasma cell leukemia, amyloid light-chain amyloidosis,Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Patients with known MM brain lesions or meningeal involvement
  • History of neurodegenerative condition, central nervous system (CNS) movement disorder, or patients with a history of seizure within 12 months prior to study enrollment are excluded.
  • Continuous systemic corticosteroid treatment with more than 10 mg of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
  • Treatment with any systemic standard or investigational anti-myeloma therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter.
  • Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bispecific antibody) or BCMA-directed CAR T therapy
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; or other uncontrolled infection
  • Has known allergy or hypersensitivity to components of REGN5458
  • History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
  • Known hypersensitivity to both allopurinol and rasburicase
  • Pregnant or breastfeeding women
  • Women of childbearing potential and men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
  • Another malignancy in the past 5 years, with the exception of non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.

Note: Other protocol defined inclusion / exclusion criteria apply

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Verified Winship Cancer Institute of Emory University

SparkCures Verified Accurate, up-to-date information. Learn more

Norton Cancer Institute St. Matthews Campus

Louisville, KY

Rutgers Cancer Institute of New Jersey Rutgers, The State University of New Jersey

New Brunswick, NJ

Verified Winship Cancer Institute of Emory University

SparkCures Verified Accurate, up-to-date information. Learn more

Norton Cancer Institute St. Matthews Campus

Louisville, KY

New Jersey
Rutgers Cancer Institute of New Jersey Rutgers, The State University of New Jersey

New Brunswick, NJ

New York

Published Results

BCMA/CD3 Bispecific Antibody REGN5458 Elicits Early, Deep Responses in Relapsed/Refractory Myeloma

December 05, 2020

Results indicated that 95% (n = 18) of 19 patients who responded to treatment experienced a very good partial response (VGPR) or better and 42% achieved a complete response (CR) or a stringent CR (sCR).

At a median follow-up of 2.6 months, patients who received the agent at a dose of 3 mg, 6 mg, or 12 mg (n = 24; dosing levels [DL] 1-3) experienced an overall response rate (ORR) of 29.2%; 20.9% of these responders experienced a CR or sCR, while 4.2% had VGPR or better and 4.2% achieved a partial response (PR).

The ORR was higher among those who received REGN5458 at a dose of 24 mg or 48 mg (n = 17; DL 4-5), at 41.2%, with 11.8% of patients collectively experiencing a CR (11.8%)/sCR (5.9%) and 23.5% of patients achieving a VGPR. Patients who received 96 mg (n = 8; DL 6), the highest dose of the antibody evaluated on the trial, experienced the highest ORR, at 62.5%; all of these patients had a VGPR.

First Clinical Data for REGN5458 (BCMAxCD3) Show Positive Preliminary Results in Multiple Myeloma

December 08, 2019

Results were presented today at the American Society of Hematology (ASH) Annual Meeting from the first two dose groups (3 mg and 6 mg weekly doses).

  • Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment.
  • Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group.
  • In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD) negative, meaning that no cancer cells were detectable in their bone marrow.


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