Clinical Trials /

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

NCT03761108

Description:

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). In the phase 2 portion of the study: To assess the anti-tumor activity of REGN5458 as measured by objective response rate (ORR) The secondary objectives of the study are: In the phase 1 dose escalation portion: - To assess the preliminary anti-tumor activity of REGN5458 as measured by ORR, duration of response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS) - To evaluate the pharmacokinetic (PK) properties of REGN5458 - To characterize the immunogenicity of REGN5458 In the phase 2 portion only: - To assess the anti-tumor activity of REGN5458 as measured by ORR, DOR, PFS, rate of MRD negative status, and OS - To evaluate the effects of REGN5458 on patient-reported quality of life, functions and symptoms - To evaluate the safety and tolerability of REGN5458 - To evaluate the PK properties of REGN5458 - To characterize the immunogenicity of REGN5458

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First in Human (FIH) Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: R5458-ONC-1826
  • SECONDARY ID: 2018-003188-78
  • NCT ID: NCT03761108

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
REGN5458REGN5458

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
REGN5458ExperimentalCohorts of multiple REGN5458 dose levels
  • REGN5458

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
Time Frame:Up to 28 days
Safety Issue:
Description:In the Phase 1 portion

Secondary Outcome Measures

Measure:Concentrations of REGN5458 in the serum over time
Time Frame:Up to 64 weeks
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:Incidence over time of treatment-emergent anti-drug antibodies (ADA) to REGN5458
Time Frame:Up to 64 weeks
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:Duration of response (DOR) using the IMWG criteria
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:Progression-free survival (PFS) as measured using the IMWG criteria
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:Rate of minimal residual disease (MRD) negative status using the IMWG criteria
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:Overall survival (OS)
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 1 and phase 2 portions
Measure:ORR as measured using the IMWG criteria
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 1 portion
Measure:Incidence and severity of TEAEs
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 2 portion
Measure:Incidence and severity of AESIs
Time Frame:Up to 14 months after the last dose
Safety Issue:
Description:In the phase 2 portion

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • Relapsed, Refractory

Last Updated

October 31, 2019