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

• ClinicalTrials.gov Identifier: NCT04083534
• Recruitment Status: Recruiting
• First Posted: September 10, 2019
• Last Update Posted: June 26, 2020
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, Indiana

Regeneron Study SIte; Recruiting

Indianapolis, Indiana, United States, 46202

United States, Michigan

Regeneron Study Site; Recruiting

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Regeneron Study Site; Recruiting

Rochester, Minnesota, United States, 55905

United States, Texas

Regeneron Study Site; Recruiting

Houston, Texas, United States, 77030

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trials Investigator; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04083534
• Other Study ID Numbers: R5459-ONC-1888; 2019-001108-39 ( EudraCT Number )
• First Posted: September 10, 2019
• Last Update Posted: June 26, 2020
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant 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