REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Participants With Relapsed/Refractory Multiple Myeloma

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05137054
Collaborator
(none)
256
4
4
94.7
64
0.7

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the safety and tolerability, and identify the recommended dose of REGN5458 for the expansion portion in combination with each one of the following cancer treatments:

  • Daratumumab plus dexamethasone (Dd: Cohort 1)

  • Carfilzomib plus dexamethasone (Kd: Cohort 2)

  • Lenalidomide plus dexamethasone (Rd: Cohort 3)

  • Bortezomib plus dexamethasone Vd: (Cohort 4)

The secondary objectives of the study for each cohort are:
  • To assess the preliminary anti-tumor activity by International Myeloma Working Group (IMWG) criteria

  • To measure the depth and durability of response

  • To evaluate the pharmacokinetic (PK) properties of REGN5458 when given in combination with Dd, Kd, Rd, and Vd

  • To evaluate immunogenicity of REGN5458 when given in combination with Dd, Kd, Rd, and Vd

  • Describe the overall survival (OS) of the participants

Study Design

Study Type:
Interventional
Anticipated Enrollment :
256 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Feb 27, 2025
Anticipated Study Completion Date :
Jul 23, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1: R5458 + Dd Combo

R5458 + Daratumumab and dexamethasone (Dd)

Drug: REGN5458
REGN5458 is administered by intravenous (IV) infusion

Drug: Daratumumab
Daratumumab is administered by IV infusion and/or subcutaneous (SC) injection; SC injection is administered after a minimum of 2 cycles of IV administration at the investigator's discretion.
Other Names:
  • Darzalex®; Darzalex Faspro™
  • Drug: Dexamethasone
    Dexamethasone is administered by mouth as a capsule or by IV administration.
    Other Names:
  • Decadron®
  • Experimental: Cohort 2: R5458 + Kd Combo

    R5458 + Carfilzomib and dexamethasone (Kd)

    Drug: REGN5458
    REGN5458 is administered by intravenous (IV) infusion

    Drug: Carfilzomib
    Carfilzomib is administered by IV infusion
    Other Names:
  • Kyprolis®
  • Drug: Dexamethasone
    Dexamethasone is administered by mouth as a capsule or by IV administration.
    Other Names:
  • Decadron®
  • Experimental: Cohort 3: R5458 + Rd Combo

    R5458 + Lenalidomide and dexamethasone (Rd)

    Drug: REGN5458
    REGN5458 is administered by intravenous (IV) infusion

    Drug: Lenalidomide
    Lenalidomide is administered by mouth (PO) as a capsule
    Other Names:
  • Revlimid®
  • Drug: Dexamethasone
    Dexamethasone is administered by mouth as a capsule or by IV administration.
    Other Names:
  • Decadron®
  • Experimental: Cohort 4: R5458 + Vd Combo

    R5458 + Bortezomib and dexamethasone (Vd)

    Drug: REGN5458
    REGN5458 is administered by intravenous (IV) infusion

    Drug: Bortezomib
    Bortezomib is administered by IV infusion or SC injection
    Other Names:
  • Velcade®
  • Drug: Dexamethasone
    Dexamethasone is administered by mouth as a capsule or by IV administration.
    Other Names:
  • Decadron®
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of pre-defined safety criteria (dose-limiting toxicities (DLTs)) from the first dose through the end of the DLT observation period [Up to 28 Days]

      Dose finding portion only

    2. Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 5 Years]

      Dose finding portion Dose expansion portion

    3. Incidence and severity of serious adverse events (SAEs) [Up to 5 Years]

      Dose finding portion Dose expansion portion

    4. Incidence and severity of adverse events of special interest (AESIs) [Up to 5 Years]

      Dose finding portion Dose expansion portion

    5. Incidence of laboratory abnormalities [Up to 5 Years]

      As measured by chemistry, hematology, urinalysis and pregnancy testing Dose finding portion Dose expansion portion

    Secondary Outcome Measures

    1. Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria [Up to 5 Years]

      Dose finding portion Dose expansion portion

    2. Duration of response (DOR) using the IMWG criteria [Up to 5 Years]

      Dose finding portion Dose expansion portion

    3. Progression-free survival (PFS) as measured using the IMWG criteria [Up to 5 Years]

      Dose finding portion Dose expansion portion

    4. Rate of minimal residual disease (MRD) negative status using the IMWG criteria [Up to 5 Years]

      Dose finding portion Dose expansion portion

    5. Concentrations of REGN5458 in the serum over time [Up to 5 Years]

      Dose finding portion Dose expansion portion

    6. Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [Up to 5 Years]

      Dose finding portion Dose expansion portion

    7. Overall Survival (OS) [Up to 5 Years]

      Dose finding portion Dose expansion portion

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

    2. Relapsed/refractory multiple myeloma (MM): Progression of disease following at least 3 lines of therapy, or least 2 lines of therapy and either:

    • prior exposure to at least 1 anti-CD38 antibody, 1 IMiD and 1 PI or

    • double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD. Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated. However, patients cannot be refractory to an anti-CD38 antibody-containing regimen. In addition, patients must have a 6-month washout from prior anti-CD38 antibody therapy.

    Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose. However, patients cannot be refractory to a carfilzomib-containing regimen. In addition, patients must have a 6-month washout from prior carfilzomib therapy.

    Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen that included 25 mg of lenalidomide. In addition, patients must have a 6-month washout from prior lenalidomide therapy (including maintenance therapy).

    Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen including the approved induction dose of bortezomib. In addition, patients must have a 6-month washout from prior bortezomib therapy.

    1. Participants must have measurable disease and as defined in the protocol for response assessment as per the 2016 International Myeloma Working Group (IMWG) response assessment criteria

    2. Adequate creatinine clearance, hematologic and hepatic functions, as defined in protocol

    3. Life expectancy of at least 6 months

    Key Exclusion Criteria:
    1. Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

    2. Participants with known MM brain lesions or meningeal involvement

    3. Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter.

    4. History of allogeneic stem cell transplantation, or autologous stem cell transplantation within 12 weeks of the start of study drug regimen

    5. For participants with peripheral neuropathy grade ≥2 receiving bortezomib-based treatment (cohort 4 only)

    6. Prior treatment with BCMA-directed immunotherapies, including any chimeric antigen receptor T cell (CAR T) therapy (Note: BCMA antibody-drug conjugates are not excluded)

    7. History of neurodegenerative condition or central nervous system (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded

    8. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential

    9. Cardiac ejection fraction <40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan.

    10. Pregnant or breasting feeding women or women of childbearing potential (WOCBP) with positive pregnancy test result

    11. WOCBP or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.

    NOTE: Other protocol defined inclusion/exclusion criteria apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital Universitario Marqués de Valdecilla (HUMV) Santander Cantabria Spain 39008
    2 Clinica Universidad de Navarra Pamplona Navarre Spain 31008
    3 Clinica Universidad de Navarra Madrid Spain 28027
    4 Hospital Universitario de Salamanca Salamanca Spain 37007

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05137054
    Other Study ID Numbers:
    • R5458-ONC-2012
    • 2020-004638-39
    First Posted:
    Nov 30, 2021
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Regeneron Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 19, 2022