Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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 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
Phase
Phase 1/Phase 2
Funding Agency/Sponsor
Industrial
Disease
Myeloma
Enrollment Eligibility
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 (PI). Refractory disease is defined
as lack of response or relapse within 60 days of last treatment.
- Phase 2:
1. Progression on or after at least 3 prior lines of therapy including a(n) PI,
IMiD, and anti-CD38 antibody, OR
2. 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.
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