Multiple myeloma (MM) is a plasma cell malignancy characterized by the proliferation of clonal plasma cells in the bone marrow. The disease primarily localizes to the bones and bone marrow, with resultant cytopenias, bone pain, fractures, infections, hypercalcemia, and renal failure. This study aims to evaluate the safety and change in disease activity of etentamig in combination with pomalidomide compared with standard available therapies in participants with relapsed or refractory multiple myeloma who have received 1-3 prior lines of treatment, including lenalidomide. Etentamig is an investigational drug being developed for the treatment of relapsed or refractory multiple myeloma. This is a randomized, open-label study. The study will include a safety run-in portion and a randomized portion. The safety run-in participants will receive etentamig in combination with pomalidomide. The randomized portion of the study participants will receive either etentamig with pomalidomide or Standard Available Therapies (SATs). Approximately 520 participants will be enrolled in the study at approximately 200 sites worldwide. Prior to initiation of the randomized portion of the study, the safety run-in will be conducted in which participants will receive etentamig injections plus oral pomalidomide. Following review of the safety run-in data and per protocol-defined criteria, the study will advance to the randomized portion where participants will be randomized to receive either etentamig injections plus oral pomalidomide or investigator's choice of SAT: SC daratumumab, oral pomalidomide, and oral/ IV dexamethasone (DPd); SC daratumumab, IV carfilzomib, and oral/IV dexamethasone (DKd); or SC teclistamab monotherapy. The total study duration is approximately 75 months There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
520
Injection
Oral
Injection
Oral or Injection
Injection
Injection
University of Arizona Cancer Center /ID# 285339
Tucson, Arizona, United States
Toi Clinical Research - Whittier /ID# 284462
Cerritos, California, United States
University of California Los Angeles /ID# 282444
Los Angeles, California, United States
University Of Colorado - Anschutz Medical Campus /ID# 283478
Aurora, Colorado, United States
MedStar Georgetown University Hospital /ID# 283734
Washington D.C., District of Columbia, United States
Safety Run-In: Number of Participants With Adverse Events (AE)s
AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Time frame: Up to Approximately 75 Months
Randomized Portion: Complete Response (CR) or Better Rate Per Independent Review Committee (IRC) Assessment
CR or better is defined as proportion of participants with best overall response (BOR) of CR or stringent CR (sCR) as assessed per International Myeloma Working Group (IMWG) 2016 criteria. CR is defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and less than 5% plasma cells in bone marrow aspirates. The treatment effect will be summarized as the difference in the CR or better rates between etentamig in combination with pomalidomide and standard available therapies (SAT).
Time frame: Up to Approximately 75 Months
Randomized Portion: Progression-Free Survival (PFS) Per Independent Review Committee (IRC) Assessment
PFS is defined as duration from the date of randomization to the date of disease progression assessed according to the IMWG (2016) response criteria, per IRC assessment or death due to any cause, whichever occurs first.
Time frame: Up to Approximately 75 Months
Safety Run-In: Best Overall Response (BOR) of Per Investigator Assessment
BOR is defined as the best response achieved across all response assessments, partial response (PR) + very good partial response (VGPR) + complete response (CR) + stringent complete response (sCR), from randomization until disease progression per investigator assessment, using IMWG (2016) response criteria.
Time frame: Up to Approximately 75 Months
Safety Run-In: Maximum Observed Concentration (Cmax) of Etentamig
Cmax of Etentamig.
Time frame: Up to Approximately 12 Months
Safety Run-In: Time to Cmax (Tmax) of Etentamig
Cmax of Etentamig.
Time frame: Up to Approximately 12 Months
Safety Run-In: Area under the Serum Concentration-Time Curve (AUC) of Etentamig
Cmax of Etentamig.
Time frame: Up to Approximately 12 Months
Safety Run-In: Immunogenicity of Etentamig
Immunogenicity of etentamig is defined as the summary of antidrug antibody (ADA) status, ADA titers, and neutralizing antibody (NAb)s, if NAb samples are analyzed.
Time frame: Up to Approximately 75 Months
Randomized Portion: Minimal Residual Disease Negative Complete Response (MRDnegCR) Per IRC Assessment
MRDnegCR is defined as achievement of CR or better by IMWG (2016) response criteria per IRC assessment and MRD negative status as assessed by next-generation sequencing (NGS) at threshold defined in the protocol.
Time frame: Up to Approximately 75 Months
Randomized Portion: Overall Survival (OS)
Overall Survival (OS) is defined as the duration from the date of randomization to the date of death from any cause.
Time frame: Up to Approximately 75 Months
Randomized Portion: Sustained Minimal Residual Disease (MRD) Negativity
Sustained MRD negativity assessed in participants with relapsed/refractory multiple myeloma (RRMM).
Time frame: Up to Approximately 75 Months
Randomized Portion: Best Minimal Residual Disease Negative Complete Response (MRD Negative CR) Per IRC Assessment
Best MRD negative CR per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM).
Time frame: Up to Approximately 75 Months
Randomized Portion: BOR Per IRC Assessment
BOR is defined as the best response achieved across all response assessments, PR + VGPR + CR +sCR from randomization until disease progression per IRC assessment, using IMWG (2016) response criteria.
Time frame: Up to Approximately 75 Months
Randomized Portion: VGPR or Better Rate Per IRC Assessment
VGPR or better rate per IRC assessment, defined as percentage of participants achieving VGPR, CR, or sCR using IMWG (2016) response criteria.
Time frame: Up to Approximately 75 Months
Randomized Portion: Time to Response (TTR) Per IRC Assessment
TTR is defined as the time from randomization to first documented response (PR or better) per IRC assessment using IMWG (2016) response criteria.
Time frame: Up to Approximately 75 Months
Randomized Portion: Duration of Response (DOR) Per IRC Assessment
DOR is defined as the time from first documented response (PR or better) to disease progression or death, whichever occurs first, per IRC assessment using IMWG (2016) response criteria.
Time frame: Up to Approximately 75 Months
Randomized Portion: Second Progression-Free Survival (PFS2)
PFS2 is defined as time from randomization to second disease progression or death from any cause, whichever occurs first.
Time frame: Up to Approximately 75 Months
Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (QoL) Score
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life score. Patient-reported outcome (PRO) assessment.
Time frame: Up to Approximately 75 Months
Randomized Portion: Event-Free Survival (EFS) Per IRC Assessment
EFS per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM).
Time frame: Up to Approximately 75 Months
Randomized Portion: Time to Next Treatment (TTNT)
TTNT is defined as time from randomization to initiation of next anti-myeloma therapy.
Time frame: Up to Approximately 75 Months
Randomized Portion: Time to Symptomatic Disease Progression
Time to symptomatic disease progression in participants with relapsed/refractory multiple myeloma (RRMM).
Time frame: Up to Approximately 75 Months
Randomized Portion: Change From Baseline in Disease Symptoms as Measured by the Disease Symptoms Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Myeloma Module (EORTC QLQ-MY20)
Change from baseline in disease symptoms as measured by the disease symptoms domain of the EORTC QLQ-MY20 .
Time frame: Up to Approximately 75 Months
Randomized Portion: Change From Baseline in Physical Functioning as Measured by the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Change from baseline at 6 months in physical functioning as measured by the physical functioning domain of the EORTC QLQ-C30.
Time frame: Up to Approximately 75 Months
Randomized Portion: Overall Bother Due to Treatment Side Effects as Assessed by the Functional Assessment of Cancer Therapy - General Population, Item 5 (FACT-G GP5)
Overall bother due to treatment side effects as assessed by the Functional Assessment of Cancer Therapy - General Population, Item 5 FACT-G GP5. Patient-reported outcome (PRO) assessment.
Time frame: Up to Approximately 75 Months
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