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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 387

Inclusion Criteria

1. Age =18 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status =1.

3. Confirmed diagnosis of active MM by IMWG diagnostic criteria.

4. Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria.

5. Phase 1 Part 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:
a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor (PI), an IMiD, and an anti-CD38 antibody, OR
b. Progression on or after an anti-CD38 antibody and have disease that is double refractory” to a PI 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 PI. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.

6. Phase 1 Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
*Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.

Phase 2 (Cohorts 1 and 2): Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. *Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.

Phase 2 (Cohort 3): Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. *Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
AND if they have relapsed after a BCMA-directed CAR-T cellular therapy then:
• Treatment with a CAR-T must have been associated with a response of PR or better, and
• If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with REGN5458.

NOTE: Other protocol-defined Inclusion Criteria apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 387
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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).

2. Patients with known MM brain lesions or meningeal involvement.

3. 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.

4. 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 Exclusion criteria apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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