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

NCT04083534 | Completed Phase 1 FDA Drug

• 2 other identifiers: R5459-ONC-18882019-001108-39
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

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) 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. 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 pharmacokinetic (PK) properties of REGN5459
• To characterize the immunogenicity of REGN5459
• To evaluate the effects of REGN5459 on patient-reported quality of life (QoL), symptoms, functioning and general health status 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.

Conditions

Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period

  Phase 1

  Up to 35 Days

• Incidence and severity of treatment-emergent adverse events (TEAEs) during REGN5459 treatment period

  Phase 1

  Up to 12 Weeks After the Last Dose

• Incidence and severity of adverse events of special interest (AESI) with REGN5459 treatment period

  Phase 1

  Up to 12 Weeks After the Last Dose

• Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria

  Phase 2

  Up to Approximately 104 Weeks

Secondary Outcomes (15)

• Concentrations of REGN5459 in the serum over time

  Up to 12 Weeks After the Last Dose

• Incidence over time of anti-drug antibodies (ADAs) to REGN5459

  Up to 12 Weeks After the Last Dose

• Duration of response (DOR) using the IMWG criteria

  Up to Approximately 104 Weeks

• Progression-free survival (PFS) as measured using the IMWG criteria

  Up to Approximately 104 Weeks

• Rate of minimal residual disease (MRD) negative status using the IMWG criteria

  Up to Approximately 104 Weeks

Study Arms (1)

REGN5459

EXPERIMENTAL

Cohorts of multiple REGN5459 dose levels

Drug: REGN5459

Interventions

REGN5459 DRUG

Administered by intravenous (IV) infusion

REGN5459

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Patients must have myeloma that is response-evaluable according to the 2016 International Myeloma Working Group (IMWG) response criteria
• Measurable disease is defined as 1 or more of the following:
• Serum M-protein ≥1 g/dL,
• Urine M-protein ≥200 mg/24-hour, and/or
• Free light chain (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 ≥400 mg/dL 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 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 imide drug (IMiD), and an anti-CD38 antibody, OR
• Progression on or after an anti-CD38 antibody and having 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:
• Platelet count \> 50 x 109/L. A patient may not have received a platelet transfusion within 7 days to meet this platelet eligibility requirement.
• ANC \> 1.0 x 109/L. A patient may not have received granulocyte colony stimulating factor (G-CSF) within 2 days to meet this absolute neutrophil count eligibility requirement.
• Hemoglobin \> 8.0 g/dL

You may not qualify if:

• Patients with known MM brain lesions or meningeal involvement
• History of neurodegenerative condition or central nervous system (CNS) movement disorder, or patients with a history of seizure within 12 months before study enrollment are excluded
• 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
• 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.
• 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.
• Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by polymerase chain reaction (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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (7)

Regeneron Study Site

Indianapolis, Indiana, 46202, United States

Location

Regeneron Study Site

Ann Arbor, Michigan, 48109, United States

Location

Regeneron Study Site

Rochester, Minnesota, 55905, United States

Location

Regeneron Study Site

New York, New York, 10029, United States

Location

Regeneron Study Site

Dallas, Texas, 75390, United States

Location

Regeneron Study Site

Houston, Texas, 77030, United States

Location

Regeneron Study Site

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials Investigator

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: September 10, 2019
• Study Start: September 26, 2019
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: May 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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).

Locations

US (7)