Phase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma
About the study
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 for each cohort: To assess the anti-tumor activity of REGN5458, as measured by objective response rate (ORR) and as 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 drug (IMiD), and anti-CD38 monoclonal antibody)
Applicable to the phase 2 Japan cohort only: In addition to the objectives in phase 2, the Japan cohort will also assess the safety, tolerability, DLTs, and pharmacokinetics (PK) of different regimens of REGN5458 as a monotherapy in Japanese patients.
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 PK properties of REGN5458
To characterize the immunogenicity of REGN5458
In the phase 2 portion for each cohort:
To assess the anti-tumor activity of REGN5458 as measured by:
ORR, as determined by the investigator
DOR and PFS, as determined by an IRC and the investigator
Rate of MRD negative status
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
Who can take part
You may be eligible to participate in the study if you meet the following criteria:
INCLUSION 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:
- 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
- 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 (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
Phase 2:
- Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
- 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.
Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy.
EXCLUSION CRITERIA
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
- Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)
- 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
Study Locations
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How to Apply
Contact the study center to learn if this study is a good match for you.
Study’s details
Contition
Multiple Myeloma
Age (in years)
18+
Phase
Phase 1/Phase 2
Participants needed
309
Est. Completion Date
Mar 14, 2032
Treatment type
Interventional
Sponsor
Regeneron Pharmaceuticals
ClinicalTrials.gov identifier
NCT03761108
Study number
R5458-ONC-1826
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