Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03761108
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

The primary objectives of the study are:

In the Phase 1 portion of the study: 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 all therapeutic options that are expected to provide meaningful clinical benefit. The determination of the RP2DR will be based on the review of non-clinical and all clinical data, including that pertaining to safety, pharmacokinetics (PK), PK/PD (pharmacokinetic/pharmacodynamic) relationships, and efficacy.

In the Phase 2 portion of the study: To assess the preliminary anti-tumor activity of REGN5458 as measured by objective response rate (ORR)

The secondary objectives of the study are:

In the phase 1 and phase 2 portion:

  • To assess the preliminary anti-tumor activity of REGN5458 as measured by duration of response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS)
  • To evaluate the (PK) properties of REGN5458
  • To characterize the immunogenicity of REGN5458

In the Phase 1 portion only:

  • To assess the preliminary anti-tumor activity of REGN5458 as measured by ORR

In the Phase 2 portion only:

  • To evaluate the safety and tolerability of REGN5458

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: REGN5458 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : December 16, 2022
Estimated Study Completion Date : December 16, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: REGN5458
Cohorts of multiple REGN5458 dose levels
Drug: REGN5458
Administered by intravenous (IV) infusion




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [ Time Frame: Up to 28 days ]
    In the Phase 1 portion

  2. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 14 months after the last dose ]
    In the Phase 1 portion

  3. Incidence and severity of adverse events of special interest (AESIs) [ Time Frame: Up to 14 months after the last dose ]
    In the Phase 1 portion

  4. Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 14 months after the last dose ]
    In the Phase 2 portion


Secondary Outcome Measures :
  1. Concentrations of REGN5458 in the serum over time [ Time Frame: Up to 64 weeks ]
    In the phase 1 and phase 2 portions

  2. Incidence over time of treatment-emergent anti-drug antibodies (ADA) to REGN5458 [ Time Frame: Up to 64 weeks ]
    In the phase 1 and phase 2 portions

  3. Duration of response (DOR) using the IMWG criteria [ Time Frame: Up to 14 months after the last dose ]
    In the phase 1 and phase 2 portions

  4. Progression-free survival (PFS) as measured using the IMWG criteria [ Time Frame: Up to 14 months after the last dose ]
    In the phase 1 and phase 2 portions

  5. Rate of minimal residual disease (MRD) negative status using the IMWG criteria [ Time Frame: Up to 14 months after the last dose ]
    In the phase 1 and phase 2 portions

  6. Overall survival (OS) [ Time Frame: Up to 14 months after the last dose ]
    In the phase 1 and phase 2 portions

  7. ORR as measured using the IMWG criteria [ Time Frame: Up to 14 months after the last dose ]
    In the phase 1 portion

  8. Incidence and severity of TEAEs [ Time Frame: Up to 14 months after the last dose ]
    In the phase 2 portion

  9. Incidence and severity of AESIs [ Time Frame: Up to 14 months after the last dose ]
    In the phase 2 portion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 symptomatic myeloma at the time of study entry with myeloma-related organ damage or tissue dysfunction
  • Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chain (FLC)
  • A patient with non-secretory MM may be considered for enrollment after discussion with the sponsor that includes the feasibility of the plan for response assessment according to IMWG guidelines
  • Disease progression based on IMWG criteria
  • 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 or refusal of the therapy and including either:
  • 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
  • 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.
  • Adequate hematologic and hepatic function
  • Serum creatinine clearance by Cockcroft-Gault >30 mL/min

Key Exclusion Criteria:

  • Presence of plasma cell leukemia, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Patients with known MM brain lesions or meningeal involvement with MM
  • History of neurodegenerative condition or central nervous system (CNS) movement disorder
  • 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 prior to 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
  • A severe allergic reaction is defined for this purpose as that which has met criteria for common terminology criteria for adverse events (CTCAE) v5.0 grade 3 or grade 4 severity (ie, characterized by bronchospasm; or life-threatening consequences; or requiring intravenous (IV) intervention, other urgent intervention, or hospitalization for clinical sequelae) or that has required an emergency room visit.
  • 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.

Note: Other protocol defined inclusion / exclusion criteria apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03761108


Contacts
Layout table for location contacts
Contact: Clinical Trial Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
Layout table for location information
United States, Florida
Regeneron Study Site Recruiting
Miami, Florida, United States, 33136
Regeneron Study Site Recruiting
Tampa, Florida, United States, 33612
United States, Kentucky
Regeneron Study Site Recruiting
Louisville, Kentucky, United States, 40207
United States, Michigan
Regeneron Study Site Recruiting
Detroit, Michigan, United States, 48201
United States, New Jersey
Regeneron Study Site Recruiting
New Brunswick, New Jersey, United States, 08901
United States, New York
Regeneron Study Site Recruiting
New York, New York, United States, 10029
Regeneron Study Site Recruiting
New York, New York, United States, 10032-3729
United States, Ohio
Regeneron Study Site Recruiting
Columbus, Ohio, United States, 43210
United States, Washington
Regeneron Study Site Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Trial Management Regeneron Pharmaceuticals

Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03761108     History of Changes
Other Study ID Numbers: R5458-ONC-1826
2018-003188-78 ( EudraCT Number )
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
URL: https://errs.regeneron.com/external

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Relapsed, Refractory
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases