Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
Relapsed or Refractory Multiple Myeloma, Etentamig, Pomalidomide, Cancer
Brief summary
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.
Interventions
DRUGEtentamig
Injection
DRUGPomalidomide
Oral
DRUGDaratumumab
Injection
DRUGDexamethasone
Oral or Injection
DRUGCarfilzomib
Injection
DRUGTeclistamab
Injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of relapsed or refractory (RR) multiple myeloma (MM). * Prior treatment with at least one and no more than three prior lines of therapy, including lenalidomide. * Adequate organ function and performance status
Exclusion criteria
* Prior B-cell maturation antigen (BCMA) directed T-cell engager therapy (bispecific or trispecific) * Known central nervous system involvement of MM * Known history of other active malignancies within the past 3 years (with specific exceptions) * Clinically significant conditions (renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary, or hepatic disease within the last 6 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-In: Number of Participants With Adverse Events (AE)s | Up to Approximately 75 Months | 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. |
| Randomized Portion: Complete Response (CR) or Better Rate Per Independent Review Committee (IRC) Assessment | Up to Approximately 75 Months | 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). |
| Randomized Portion: Progression-Free Survival (PFS) Per Independent Review Committee (IRC) Assessment | Up to Approximately 75 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-In: Best Overall Response (BOR) of Per Investigator Assessment | Up to Approximately 75 Months | 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. |
| Safety Run-In: Maximum Observed Concentration (Cmax) of Etentamig | Up to Approximately 12 Months | Cmax of Etentamig. |
| Safety Run-In: Time to Cmax (Tmax) of Etentamig | Up to Approximately 12 Months | Cmax of Etentamig. |
| Safety Run-In: Area under the Serum Concentration-Time Curve (AUC) of Etentamig | Up to Approximately 12 Months | Cmax of Etentamig. |
| Safety Run-In: Immunogenicity of Etentamig | Up to Approximately 75 Months | 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. |
| Randomized Portion: Minimal Residual Disease Negative Complete Response (MRDnegCR) Per IRC Assessment | Up to Approximately 75 Months | 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. |
| Randomized Portion: Overall Survival (OS) | Up to Approximately 75 Months | Overall Survival (OS) is defined as the duration from the date of randomization to the date of death from any cause. |
| Randomized Portion: Sustained Minimal Residual Disease (MRD) Negativity | Up to Approximately 75 Months | Sustained MRD negativity assessed in participants with relapsed/refractory multiple myeloma (RRMM). |
| Randomized Portion: Best Minimal Residual Disease Negative Complete Response (MRD Negative CR) Per IRC Assessment | Up to Approximately 75 Months | Best MRD negative CR per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM). |
| Randomized Portion: BOR Per IRC Assessment | Up to Approximately 75 Months | 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. |
| Randomized Portion: VGPR or Better Rate Per IRC Assessment | Up to Approximately 75 Months | VGPR or better rate per IRC assessment, defined as percentage of participants achieving VGPR, CR, or sCR using IMWG (2016) response criteria. |
| Randomized Portion: Time to Response (TTR) Per IRC Assessment | Up to Approximately 75 Months | TTR is defined as the time from randomization to first documented response (PR or better) per IRC assessment using IMWG (2016) response criteria. |
| Randomized Portion: Duration of Response (DOR) Per IRC Assessment | Up to Approximately 75 Months | 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. |
| Randomized Portion: Second Progression-Free Survival (PFS2) | Up to Approximately 75 Months | PFS2 is defined as time from randomization to second disease progression or death from any cause, whichever occurs first. |
| Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (QoL) Score | Up to Approximately 75 Months | 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. |
| Randomized Portion: Event-Free Survival (EFS) Per IRC Assessment | Up to Approximately 75 Months | EFS per IRC assessment in participants with relapsed/refractory multiple myeloma (RRMM). |
| Randomized Portion: Time to Next Treatment (TTNT) | Up to Approximately 75 Months | TTNT is defined as time from randomization to initiation of next anti-myeloma therapy. |
| Randomized Portion: Time to Symptomatic Disease Progression | Up to Approximately 75 Months | Time to symptomatic disease progression in participants with relapsed/refractory multiple myeloma (RRMM). |
| 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) | Up to Approximately 75 Months | Change from baseline in disease symptoms as measured by the disease symptoms domain of the EORTC QLQ-MY20 . |
| 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) | Up to Approximately 75 Months | Change from baseline at 6 months in physical functioning as measured by the physical functioning domain of the EORTC QLQ-C30. |
| 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) | Up to Approximately 75 Months | 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. |
Countries
Australia, Canada, France, Germany, Hungary, Italy, Netherlands, Norway, Portugal, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed