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First in Human (FIH) Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma (LINKER-MM1)

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: NCT03761108
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

The primary objectives of the study are:

In the phase 1 portion of the study: To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose regimens (RP2DRs) of REGN5458 as monotherapy in patients with relapsed or refractory multiple myeloma (MM).

In the phase 2 portion of the study: To assess the anti-tumor activity of REGN5458 as measured by objective response rate (ORR) and as separately in cohorts 1 and 2, determined by an Independent Review Committee (IRC) in patients who have progressed on or after 3 prior lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome inhibitor (PI), immunomodulatory imide (IMiD) drug (s), and anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody).

The secondary objectives of the study are:

In the phase 1 dose escalation portion:

  • To assess the preliminary anti-tumor activity of REGN5458 as determined by the investigator and measured by ORR, 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 REGN5458
  • To characterize the immunogenicity of REGN5458

In the phase 2 for each cohort:

  • To assess the anti-tumor activity of REGN5458 as measured by: ORR, DOR, PFS, as determined by an IRC and the investigator, rate of MRD negative status and OS
  • To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported functions and symptoms
  • To evaluate the safety and tolerability of REGN5458
  • To evaluate the PK properties of REGN5458
  • To characterize the immunogenicity of REGN5458

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: REGN5458 Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 291 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : May 26, 2023
Estimated Study Completion Date : October 11, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: REGN5458
Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met
Drug: REGN5458
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 ]
    In the phase 1 portion

  2. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]
    In the phase 1 portion

  3. Incidence and severity of adverse events of special interest (AESI) [ Time Frame: Up to 5 years ]
    In the phase 1 portion

  4. Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 5 years ]

    In the phase 2 portion

    Determined by blinded Independent Review Committee (IRC).



Secondary Outcome Measures :
  1. Concentrations of REGN5458 in the serum over time [ Time Frame: Up to 5 years ]
    In the phase 1 and phase 2 portions

  2. Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [ Time Frame: Up to 5 years ]
    In the phase 1 and Phase 2 portions

  3. Duration of response (DOR) using the IMWG criteria [ Time Frame: Up to 5 years ]
    In the phase 1 and Phase 2 portions

  4. Progression-free survival (PFS) as measured using the IMWG criteria [ Time Frame: Up to 5 years ]
    In the phase 1 and Phase 2 portions

  5. Rate of minimal residual disease (MRD) negative status using the IMWG criteria [ Time Frame: Up to 5 years ]
    In the phase 1 and Phase 2 portions

  6. Overall survival (OS) [ Time Frame: Up to 5 years ]
    In the phase 1 and Phase 2 portions

  7. ORR as measured using the IMWG criteria [ Time Frame: Up to 5 years ]

    In the phase 1 and Phase 2 portions

    As determined by the Investigator


  8. Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Up to 5 years ]

    In the phase 2 portion

    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."


  9. Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20]) [ Time Frame: Up to 5 years ]

    In the phase 2 portion

    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.


  10. Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L]) [ Time Frame: Up to 5 years ]

    In the phase 2 portion

    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.


  11. Change in patient-reported global health status/QoL per EORTC QLQ-C30 [ Time Frame: Baseline up to Up to 5 years ]
    In the phase 2 portion

  12. Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]
    In the phase 2 portion

  13. Effects of REGN5458 on general health status per EQ-5D-3L [ Time Frame: Up to 5 years ]
    In the phase 2 portion

  14. Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]
    In the phase 2 portion

  15. Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 [ Time Frame: Up to 5 years ]
    In the phase 2 portion

  16. Incidence and severity of TEAEs with REGN5458 [ Time Frame: Up to 5 years ]
    In the phase 2 portion

  17. Incidence and severity of AESIs with REGN5458 [ Time Frame: Up to 5 years ]
    In the phase 2 portion



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.


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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
  • Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
  • Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
  • Phase 1 Dose Escalation: 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 agent (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.

      Phase 2:

    3. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD. In addition, patients must be penta-exposed (ie, having prior exposure to 2 PIs, 2 IMiDs [lenalidomide and pomalidomide], and 1 anti-CD38 monoclonal antibody).

Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy.

Key Exclusion Criteria:

  • Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Patients with known MM brain lesions or meningeal involvement
  • Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs, and BCMA CAR T cells. Note: BCMA antibody-drug conjugates are not excluded
  • 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): NCT03761108


Contacts
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Contact: Clinical Trial Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03761108    
Other Study ID Numbers: R5458-ONC-1826
2018-003188-78 ( EudraCT Number )
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Relapsed, Refractory
Additional relevant MeSH terms:
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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