Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma
Summary
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)
Arms & interventions
- DrugLinvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
- DrugDaratumumab
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.
- DrugCarfilzomib
Carfilzomib is administered by IV infusion
- DrugLenalidomide
Lenalidomide is administered by mouth (PO) as a capsule
- DrugBortezomib
Bortezomib is administered by IV infusion or SC injection
- DrugPomalidomide
Pomalidomide is administered by mouth (PO) as a capsule
- DrugIsatuximab
Isatuximab is administered by IV infusion
- DrugFianlimab
Fianlimab is administered by IV infusion
- DrugCemiplimab
Cemiplimab is administered by IV infusion
- DrugNirogacestat
Nirogacestat is administered by mouth (PO) as a tablet
- DrugCevostamab
Cevostamab is administered by IV infusion
Outcome measures
Primary
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
Secondary
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
Eligibility criteria
Study locations (13)
Scripps Clinic Torrey Pines
La Jolla, California, 92037
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30004
Indiana University Health Simon Cancer Center
Indianapolis, Indiana, 46202
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48201
Mayo Clinic
Rochester, Minnesota, 55905
Weill Cornell Medicine/New York Presbyterian Hospital
New York, New York, 10021
New York Presbyterian Hospital Columbia University Medical Center
New York, New York, 10032
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
The Ohio State University James Cancer Hospital
Columbus, Ohio, 43210
University of Texas Southwestern
Dallas, Texas, 75390
VA Puget Sound Health Care System
Seattle, Washington, 98108