REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Participants With Relapsed/Refractory Multiple Myeloma

• Status: Not yet recruiting
• Trial end date: 2030-03-16
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to assess the safety and tolerability, and identify the recommended dose of REGN5458 for the expansion portion in combination with each one of the following cancer treatments:

• Daratumumab plus dexamethasone (Dd: Cohort 1)

• Carfilzomib plus dexamethasone (Kd: Cohort 2)

• Lenalidomide plus dexamethasone (Rd: Cohort 3)

• Bortezomib plus dexamethasone Vd: (Cohort 4)

The secondary objectives of the study for each cohort are:

• To assess the preliminary anti-tumor activity by International Myeloma Working Group (IMWG) criteria

• To measure the depth and durability of response

• To evaluate the pharmacokinetic (PK) properties of REGN5458 when given in combination with Dd, Kd, Rd, and Vd

• To evaluate immunogenicity of REGN5458 when given in combination with Dd, Kd, Rd, and Vd

• Describe the overall survival (OS) of the participants

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Regeneron Pharmaceuticals
• Treatments: Bortezomib; Daratumumab; Dexamethasone; Lenalidomide

Criteria

Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

2. Relapsed/refractory multiple myeloma (MM): Progression of disease following at least 3 lines of therapy, or least 2 lines of therapy and either:

• prior exposure to at least 1 anti-CD38 antibody, 1 IMiD and 1 PI or

• double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD. Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated. However, patients cannot be refractory to an anti-CD38 antibody-containing regimen. In addition, patients must have a 6-month washout from prior anti-CD38 antibody therapy.

Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose. However, patients cannot be refractory to a carfilzomib-containing regimen. In addition, patients must have a 6-month washout from prior carfilzomib therapy.

Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen that included 25 mg of lenalidomide. In addition, patients must have a 6-month washout from prior lenalidomide therapy (including maintenance therapy).

Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen including the approved induction dose of bortezomib. In addition, patients must have a 6-month washout from prior bortezomib therapy.

3. Participants must have measurable disease and as defined in the protocol for response assessment as per the 2016 International Myeloma Working Group (IMWG) response assessment criteria

4. Adequate creatinine clearance, hematologic and hepatic functions, as defined in protocol

5. Life expectancy of at least 6 months

Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

2. Participants with known MM brain lesions or meningeal involvement

3. Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter.

4. History of allogeneic stem cell transplantation, or autologous stem cell transplantation within 12 weeks of the start of study drug regimen

5. For participants with peripheral neuropathy grade ≥2 receiving bortezomib-based treatment (cohort 4 only)

6. Prior treatment with BCMA-directed immunotherapies, including any chimeric antigen receptor T cell (CAR T) therapy (Note: BCMA antibody-drug conjugates are not excluded)

7. History of neurodegenerative condition or central nervous system (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded

8. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential

9. Cardiac ejection fraction <40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan.

10. Pregnant or breasting feeding women or women of childbearing potential (WOCBP) with positive pregnancy test result

11. WOCBP or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.

NOTE: Other protocol defined inclusion/exclusion criteria apply