Key Inclusion Criteria:
1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
2. Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working
Group (IMWG) diagnostic criteria
3. Patients must have myeloma that is response-evaluable according to the 2016 IMWG
response criteria as defined in the protocol.
- 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, an Immunomodulatory agent (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 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 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 anti-CD38 antibody, a
proteasome inhibitor, and an IMiD.
- 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.
- Phase 2 (Cohort 3):
Patients with MM whose disease meets the following criteria:
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 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, for ALL patients, 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.
Key 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
-Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 3.
Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies
and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T
treatment is not excluded in Phase 2 Cohort 3.
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 1: Other protocol defined inclusion / exclusion criteria apply Note 2: US enrollment
completed
