This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again. In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies). This study is the first time linvoseltamab will be combined with other cancer therapies. The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination. The study is looking at several other research questions, including: * How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma * What side effects may happen from taking linvoseltamab together with another cancer treatment * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
317
Linvoseltamab is administered by intravenous (IV) infusion
Daratumumab is administered by IV infusion and/or subcutaneous (SC) injection; SC injection may be used after a minimum of 2 cycles of IV administration at the investigator's discretion.
Carfilzomib is administered by IV infusion
Lenalidomide is administered by mouth (PO) as a capsule
Bortezomib is administered by IV infusion or SC injection
Pomalidomide is administered by mouth (PO) as a capsule
Isatuximab is administered by IV infusion
Fianlimab is administered by IV infusion
Cemiplimab is administered by IV infusion
Nirogacestat is administered by mouth (PO) as a tablet
Cevostamab is administered by IV infusion
Scripps Clinic Torrey Pines
La Jolla, California, United States
RECRUITINGWinship Cancer Institute of Emory University
Atlanta, Georgia, United States
RECRUITINGIndiana University Health Simon Cancer Center
Indianapolis, Indiana, United States
RECRUITINGDana Farber/Harvard Cancer Center
Boston, Massachusetts, United States
Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
Dose finding portion only
Time frame: Up to 28 Days
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 5 Years
Severity of TEAEs
Time frame: Up to 5 Years
Incidence of serious adverse events (SAEs)
Time frame: Up to 5 Years
Severity of SAEs
Time frame: Up to 5 Years
Incidence of adverse events of special interest (AESIs)
Time frame: Up to 5 Years
Severity of AESIs
Time frame: Up to 5 Years
Incidence of laboratory abnormalities
≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]
Time frame: Up to 5 Years
Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria
Time frame: Up to 5 Years
Duration of response (DOR) by IMWG criteria
Time frame: Up to 5 Years
Progression-free survival (PFS) as measured by IMWG criteria
Time frame: Up to 5 Years
Rate of minimal residual disease (MRD) negative status by IMWG criteria
Time frame: Up to 5 Years
Concentrations of total linvoseltamab in serum over time
Time frame: Up to 5 Years
Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab
Time frame: Up to 5 Years
Overall Survival (OS)
Time frame: Up to 5 Years
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Karmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGWeill Cornell Medicine/New York Presbyterian Hospital
New York, New York, United States
RECRUITINGNew York Presbyterian Hospital Columbia University Medical Center
New York, New York, United States
RECRUITINGUniversity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
RECRUITINGWake Forest University Health Sciences
Winston-Salem, North Carolina, United States
RECRUITING...and 32 more locations