Phase 1/2 Study of REGN5458 in Adult 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: June 24, 2032

Contact Information:
Clinical Trial Administrator
844-734-6643
Summary: The main purpose of this study is to learn about the safety of REGN5458 and to find out what is the best dose of REGN5458 to give to patients with multiple myeloma. An additional purpose is to look for any signs that REGN5458 can treat cancer. The study is looking at several other research questions, including: - Side effects that may be experienced by people receiving REGN5458 - How REGN5458 works in the body - How much REGN5458 is present in the blood - How REGN5458 may work to treat cancer
Eligibility: 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

3. Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)

4. 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.

5. 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