Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT04083534
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Relapsed Multiple Myeloma Refractory Multiple Myeloma Drug: REGN5459 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 FIH Study of REGN5459 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : September 26, 2019
Estimated Primary Completion Date : September 26, 2023
Estimated Study Completion Date : October 24, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: REGN5459
Cohorts of multiple REGN5459 dose levels
Drug: REGN5459
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 ]
    Phase 1

  2. Incidence and severity of treatment-emergent adverse events (TEAEs) during REGN5459 treatment period [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1

  3. Incidence and severity of adverse events of special interest (AESIs) during REGN5459 treatment period [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1

  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 ]
    Phase 2


Secondary Outcome Measures :
  1. Concentrations of REGN5459 in the serum over time [ Time Frame: Up to 64 Weeks ]
    Phase 1 and phase 2

  2. Incidence over time of treatment-emergent anti-drug antibodies (ADA) to REGN5459 [ Time Frame: Up to 64 Weeks ]
    Phase 1 and phase 2

  3. Duration of response (DOR) using the IMWG criteria [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1 and phase 2

  4. Progression-free survival (PFS) as measured using the IMWG criteria [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1 and phase 2

  5. Rate of minimal residual disease (MRD) negative status using the IMWG criteria [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1 and phase 2

  6. Overall survival (OS) [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1 and phase 2

  7. ORR as measured using the IMWG criteria [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 1

  8. Incidence and severity of TEAEs during REGN5459 treatment period [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 2

  9. Incidence and severity of AESIs during REGN5459 treatment period [ Time Frame: Up to 14 Months After the Last Dose ]
    Phase 2



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 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.


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): NCT04083534


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

Locations
Layout table for location information
United States, Indiana
Regeneron Study SIte Recruiting
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Trials Investigator Regeneron Pharmaceuticals

Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04083534     History of Changes
Other Study ID Numbers: R5459-ONC-1888
2019-001108-39 ( EudraCT Number )
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
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
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