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

ID#: NCT03761108

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: January 23, 2019

End Date: May 01, 2025

Contact Information:
Clinical Trial Administrator
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 separately in cohorts 1 and 2, 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 (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
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. 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