Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the adverse events and change in disease activity of etentamig in combination with a cereblon E3 ligase modulatory drug (CELMoD) agent in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease state will be assessed. Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Multiple doses of etentamig in combination with iberdomide will be explored. Each treatment arm receives a different dose of etentamig and iberdomide to determine a tolerable dose. Approximately 135 adult participants with R/R MM will be enrolled in the study in approximately 50 sites worldwide. In phase 1 participants will receive escalating intravenous (IV) etentamig in combination with oral iberdomide. In phase 2 participants will receive IV etentamig at one of two doses in combination with oral iberdomide, as part of the approximately 129 month study duration. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and and monitoring of side effects.
B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) or BCMA antibody-drug conjugate (ADC) are allowed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
135
Intravenous (IV) Infusion
Oral Capsule
Beverly Hills Cancer Center /ID# 266921
Beverly Hills, California, United States
RECRUITINGColorado Blood Cancer Institute /ID# 273751
Denver, Colorado, United States
RECRUITINGWashington University /ID# 266972
St Louis, Missouri, United States
RECRUITINGRutgers Cancer Institute of New Jersey /ID# 266833
New Brunswick, New Jersey, United States
Phase 1: Dose-Limiting Toxicities (DLT)s of Etentamig when given in Combination with Iberdomide in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Time frame: Up to Approximately 56 Days
Number of Participants with Adverse Events (AE)s
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Time frame: Up to Approximately 129 Months
Partial Response (PR) Response Rate (RR)
PR is defined \>= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours, if the serum and urine M-protein are unmeasurable, a \>= 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, if the serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, a \>= 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>= 30%, \>= 50% reduction in the size of soft tissue plasmacytomas is also required, if present at baseline.
Time frame: Up to 3 Years
Very Good Partial Response (VGPR) RR
VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein \< 100 mg per 24 hours, for participants in whom the only measurable disease is by serum free light chains (FLC) levels, VGPR is defined as \>= 90% decrease in the difference between involved and uninvolved FLC levels.
Time frame: Up to 3 Years
Complete Response (CR) RR
CR is defined negative immunofixation on the serum and urine (regardless of whether disease at baseline was measurable on serum, urine, both, or neither), disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in bone marrow, and for participants in whom the only measurable disease is by serum FLC levels, a normal FLC ratio is also required.
Time frame: Up to 3 Years
Stringent Complete Response (sCR) RR
sCR is defined negative immunofixation on the serum and urine (regardless of whether disease at baseline was measurable on serum, urine, both, or neither), disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in bone marrow, normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry (kappa/lambda ratio \<= 4:1 or \>= 1:2 for kappa and lambda participants, respectively, after counting \>= 100 plasma cells).
Time frame: Up to 3 Years
Overall Response Rate (ORR)
ORR (PR + VGPR + CR + sCR) will be defined as the proportion of participants who achieved a PR or better.
Time frame: Up to 3 Years
Progression-Free Survival (PFS)
PFS is defined as the number of days from the date of first dose to the date of earliest disease progression or death.
Time frame: Up to 3 Years
Duration of Response (DOR)
DOR is defined as the number of days from the date of first response (sCR, CR, VGPR, or PR) to the earliest recurrence, progressive disease, or death, whatever occurs first.
Time frame: Up to 3 Years
Time-to-Progression (TTP)
TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.
Time frame: Up to 3 Years
Minimal Residual Disease (MRD) negativity
The MRD negativity rate is defined as the proportion of participants who achieve MRD negative status.
Time frame: Up to 3 Years
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Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 270282
New York, New York, United States
RECRUITINGUniversity Of North Carolina Health Care - Hillsborough Campus /ID# 278230
Hillsborough, North Carolina, United States
RECRUITINGSwedish Medical Center - Seattle /ID# 268052
Seattle, Washington, United States
RECRUITINGBlacktown Hospital /ID# 265983
Blacktown, New South Wales, Australia
RECRUITINGWollongong Hospital /ID# 265625
Wollongong, New South Wales, Australia
RECRUITINGThe Alfred Hospital /ID# 265981
Melbourne, Victoria, Australia
RECRUITING...and 17 more locations