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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Phase 1/2 Study of Linvoseltamab in Adult Patients With Relapsed or Refractory Multiple Myeloma

Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The main purpose of this study is to learn about the safety of linvoseltamab and to find out what is the best dose of linvoseltamab to give to patients with multiple myeloma and to look for any signs that linvoseltamab can effectively treat cancer. The study is looking at several other research questions, including: * Side effects that may be experienced by people receiving linvoseltamab * How linvoseltamab works in the body * How much linvoseltamab is present in the blood * How linvoseltamab may work to treat cancer

Who May Be Eligible (Plain English)

Key Who May Qualify: 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): ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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 linvoseltamab. 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 excluded and 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 sites are active but currently not enrolling

Treatments Being Tested

DRUG

Linvoseltamab

Administered per the protocol

Locations (20)

Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Moffitt Cancer Center - McKinley Drive
Tampa, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Indiana University_Michigan Street
Indianapolis, Indiana, United States
Norton Cancer Institute
Louisville, Kentucky, United States
C. S. Mott_University of Michigan
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Center
Detroit, Michigan, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Ohio State University James Cancer Hospital
Columbus, Ohio, United States
Oregon Health and Science University (OHSU) Marquam Hill Campus
Portland, Oregon, United States
University of Texas MD Anderson Clinic
Houston, Texas, United States
Swedish Cancer Institute
Seattle, Washington, United States
ZNA Psychiatrisch Ziekenhuis Stuivenberg
Antwerp, Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium
Universitatsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
Mainz, Rhineland-Palatinate, Germany
Universitatsklinikum Wurzburg
Würzburg, Germany
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
Nagoya, Aichi-ken, Japan