Clinical Trials /

First In Human (FIH) Study of REGN5459 in Patients With Relapsed or Refractory Multiple Myeloma (MM)

NCT04083534

Description:

In the phase 1 portion of the study, the primary objectives are to assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose regimen (RP2DR) (defined as either a maximum tolerated dose regimen [MTDR] or biologically effective dose regimen [BEDR]) of REGN5459 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, pharmacokinetic (PK), PK/pharmacodynamics (PD) relationships, and efficacy. In the phase 2 portion of the study, the primary objective is to assess the preliminary anti-tumor activity of REGN5459 as measured by objective response rate (ORR). In the phase 1 and phase 2 portion, the secondary objectives of the study are: - To assess the preliminary anti-tumor activity of REGN5459 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 REGN5459 - To characterize the immunogenicity of REGN5459 In the phase 1 portion of the study only, the secondary objective of the study is to assess the preliminary anti-tumor activity of REGN5459 as measured by ORR. In the phase 2 portion of the study only, the secondary objective of the study is to evaluate the safety and tolerability of REGN5459.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First In Human (FIH) Study of REGN5459 in Patients With Relapsed or Refractory Multiple Myeloma (MM)
  • Official Title: Phase 1/2 FIH Study of REGN5459 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: R5459-ONC-1888
  • SECONDARY ID: 2019-001108-39
  • NCT ID: NCT04083534

Conditions

  • Relapsed Multiple Myeloma
  • Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
REGN5459REGN5459

Purpose

In the phase 1 portion of the study, the primary objectives are to assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose regimen (RP2DR) (defined as either a maximum tolerated dose regimen [MTDR] or biologically effective dose regimen [BEDR]) of REGN5459 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, pharmacokinetic (PK), PK/pharmacodynamics (PD) relationships, and efficacy. In the phase 2 portion of the study, the primary objective is to assess the preliminary anti-tumor activity of REGN5459 as measured by objective response rate (ORR). In the phase 1 and phase 2 portion, the secondary objectives of the study are: - To assess the preliminary anti-tumor activity of REGN5459 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 REGN5459 - To characterize the immunogenicity of REGN5459 In the phase 1 portion of the study only, the secondary objective of the study is to assess the preliminary anti-tumor activity of REGN5459 as measured by ORR. In the phase 2 portion of the study only, the secondary objective of the study is to evaluate the safety and tolerability of REGN5459.

Trial Arms

NameTypeDescriptionInterventions
REGN5459ExperimentalCohorts of multiple REGN5459 dose levels
  • REGN5459

Eligibility Criteria

        Key Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Individual cases of
             patients with ECOG 2 performance status, whose ECOG status is expected to improve as a
             consequence of effective therapy, may be discussed with the medical monitor for
             potential enrollment

          -  Patients must have symptomatic myeloma at the time of study entry with myeloma-related
             organ damage or tissue dysfunction (such as hypercalcemia, renal insufficiency, bone
             lytic lesions, or anemia)

          -  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)

          -  Measurable disease is defined as 1 or more of the following:

               1. Serum M-protein ≥1 g/dL,

               2. Urine M-protein ≥200 mg/24-hour, and/or

               3. FLC assay with involved FLC level ≥10 mg/dL with an abnormal serum FLC ratio

          -  A patient with Immunoglobulin A (IgA) myeloma but without measurable M-protein may be
             enrolled if quantitative IgA levels are elevated and can be followed longitudinally

          -  A patient with non-secretory MM may be considered for enrollment after discussion with
             the sponsor that includes the feasibility of an individualized plan for response
             assessment

          -  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:

               1. Progression on or after at least 3 lines of therapy, or intolerance of therapy,
                  including a proteasome inhibitor, an 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.

          -  Adequate hematologic function as measured by:

               1. Platelet count > 50 x 109/L. A patient may not have received a platelet
                  transfusion within 7 days in order to meet this platelet eligibility requirement.

               2. ANC > 1.0 x 109/L. A patient may not have received granulocyte colony stimulating
                  factor (G-CSF) within 2 days in order to meet this absolute neutrophil count
                  eligibility requirement.

               3. Hemoglobin > 8.0 g/dL

          -  Adequate hepatic function, defined as:

               1. Total bilirubin ≤1.5 x ULN

               2. Transaminase (ALT, AST) ≤2.5 x ULN

               3. Alkaline phosphatase ≤2.5 x ULN

          -  Patients with Gilbert syndrome do not need to meet this total bilirubin requirement
             provided that the total bilirubin is unchanged from the baseline value.

             d. Serum creatinine clearance by Cockcroft-Gault >30 mL/min

          -  A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility
             criteria may be considered for enrollment if a measured creatinine clearance (based on
             24-hour urine collection or other reliable method) is >30 mL/min

          -  Life expectancy of at least 6 months

        Key Exclusion Criteria:

          -  Patients with known MM brain lesions or meningeal involvement with MM (suspected
             central nervous system (CNS) myeloma should be excluded by radiographic imaging and/or
             lumbar puncture, as appropriate)

          -  History of neurodegenerative condition or CNS movement disorder

          -  Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan
             (MUGA)

          -  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

               1. Patients with HIV who have controlled infection (undetectable viral load and CD4
                  count above 350 cells/microliter either spontaneously or on a stable antiviral
                  regimen) are permitted.

               2. Patients with hepatitis B (Hepatitis B Surface Antigen Test positive [HepBsAg+])
                  who have controlled infection (serum HBV DNA polymerase chain reaction [PCR] that
                  is below the limit of detection AND receiving anti-viral therapy for hepatitis B)
                  are permitted.

               3. Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection
                  (undetectable HCV RNA by PCR either spontaneously or in response to a successful
                  prior course of anti-HCV therapy) are permitted.

          -  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.
      
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:Phase 1

Secondary Outcome Measures

Measure:Concentrations of REGN5459 in the serum over time
Time Frame:Up to 64 Weeks
Safety Issue:
Description:Phase 1 and phase 2
Measure:Incidence over time of treatment-emergent anti-drug antibodies (ADA) to REGN5459
Time Frame:Up to 64 Weeks
Safety Issue:
Description:Phase 1 and phase 2
Measure:Duration of response (DOR) using the IMWG criteria
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 1 and phase 2
Measure:Progression-free survival (PFS) as measured using the IMWG criteria
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 1 and phase 2
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:Phase 1 and phase 2
Measure:Overall survival (OS)
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 1 and phase 2
Measure:ORR as measured using the IMWG criteria
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 1
Measure:Incidence and severity of TEAEs during REGN5459 treatment period
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 2
Measure:Incidence and severity of AESIs during REGN5459 treatment period
Time Frame:Up to 14 Months After the Last Dose
Safety Issue:
Description:Phase 2

Details

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

Last Updated

October 7, 2019