Phase 1/2 Study of REGN5458 in Adult Patients With Relapsed or Refractory Multiple Myeloma (LINKER-MM1)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Linvoseltamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03761108

2018-003188-78 (EudraCT Number)

R5458-ONC-1826

Details and patient eligibility

About

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

Enrollment: 387 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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:

4. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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387 participants in 4 patient groups

Linvoseltamab - Phase 1

Experimental group

Description:

Phase 1 has two parts. Part 1, consists of REGN5458/linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration. Note: subcutaneous (SC) administration is not applicable for US.

Treatment:

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 1

Experimental group

Description:

Low Dose of REGN5458/linvoseltamab IV monotherapy.

Treatment:

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 2

Experimental group

Description:

High Dose of REGN5458/linvoseltamab IV monotherapy.

Treatment:

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 3

Experimental group

Description:

Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV dose of REGN5458 monotherapy. Note: Cohort 3 is not applicable for US.

Treatment:

Drug: Linvoseltamab