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

Phase 1/2 FIH Study of REGN5459 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Refractory Multiple Myeloma; Relapsed Multiple Myeloma
• Intervention / Treatment: Drug: REGN5459

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Regeneron Study Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Regeneron Study Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Regeneron Study Site
  • New York
    • New York, New York, United States, 10029
      • Regeneron Study Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Regeneron Study Site
    • Houston, Texas, United States, 77030
      • Regeneron Study Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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:

  1. Serum M-protein ≥1 g/dL,
  2. Urine M-protein ≥200 mg/24-hour, and/or
  3. 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:

  1. 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
  2. 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:

  1. Platelet count > 50 x 109/L. A patient may not have received a platelet transfusion within 7 days 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 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
• 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

  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 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

NOTE: Other protocol defined Inclusion/Exclusion Criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5459; Cohorts of multiple REGN5459 dose levels	Drug: REGN5459; Administered by intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of REGN5459 in the serum over time	Phase 1 and phase 2	Up to 12 Weeks After the Last Dose
Incidence over time of anti-drug antibodies (ADAs) to REGN5459	Phase 1 and phase 2	Up to 12 Weeks After the Last Dose
Duration of response (DOR) using the IMWG criteria	Phase 1 and phase 2	Up to Approximately 104 Weeks
Progression-free survival (PFS) as measured using the IMWG criteria	Phase 1 and phase 2	Up to Approximately 104 Weeks
Rate of minimal residual disease (MRD) negative status using the IMWG criteria	Phase 1 and phase 2	Up to Approximately 104 Weeks
Overall survival (OS)	Phase 1 and phase 2	Up to Approximately 104 Weeks
Patient-reported Quality of Life (QOL) per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	Phase 1 and phase 2 The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Up to 12 Weeks After the Last Dose
Patient-reported QOL per EORTC Quality of Life Questionnaire-Multiple Myeloma module 20 (EORTC QLQ-MY20)	Phase 1 and phase 2 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.	Up to 12 Weeks After the Last Dose
Patient-reported QOL per EuroQoL-5 Dimension-3 Level Scale (EQ-5D-3L)	Phase 1 and phase 2 The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.	Up to 12 Weeks After the Last Dose
Change in patient-reported global health status/QOL per EORTC QLQ-C30	Phase 1 and phase 2 The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Baseline up to 12 Weeks After the Last Dose
Time to definitive deterioration in patient-reported global health status/QOL per EORTC QLQ-C30	Phase 1 and phase 2 The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Up to 12 Weeks After the Last Dose
Change in patient-reported general health status per EQ-5D-3L	Phase 1 and phase 2 The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.	Baseline up to 12 Weeks After the Last Dose
ORR as measured using the IMWG criteria	Phase 1 Only	Up to Approximately 104 Weeks
Incidence and severity of TEAEs during REGN5459 treatment period	Phase 2 Only	Up to 12 Weeks After the Last Dose
Incidence and severity of AESI during REGN5459 treatment period	Phase 2 Only	Up to 12 Weeks After the Last Dose

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trials Investigator, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Estimated): August 22, 2025
• Study Completion (Estimated): November 25, 2025

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: R5459-ONC-1888; 2019-001108-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing 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.
• IPD Sharing 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).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No