Brief Summary:
The purpose of the study is to compare Mezigdomide (CC-92480/BMS-986348) with carfilzomib and
dexamethasone (MeziKD) against carfilzomib and dexamethasone (Kd) in the treatment of RRMM:
SUCCESSOR-2.
Inclusion Criteria
- Participant has documented diagnosis of multiple myeloma and measurable disease, defined
as any of the following:.
i) Myeloma-protein (M-protein) ≥ 0.5 grams/deciliter (g/dL) by serum protein
electrophoresis (sPEP), or.
ii) M-protein ≥ 200 milligrams (mg)/24-hour urine collection by urine protein
electrophoresis (uPEP) or,.
iii) For participants without measurable disease in sPEP or uPEP: serum free light chain
levels > 100 mg/liter (L) (10 mg/dL) involved light chain and an abnormal κ/λ free light
chain ratio.
- Participant has received at least one prior line of anti-myeloma therapy. Note: One
line can contain several phases (e.g., induction, [with or without] hematopoietic stem
cell transplant, (with or without) consolidation, and/or [with or without] maintenance
therapy).
- Participant must have received prior treatment with lenalidomide and at least 2 cycles
of an anti-CD38 monoclonal antibody (mAb) (participants who were intolerant of an
anti-CD38 mAb and received < 2 cycles are still eligible).
- Participant achieved minimal response or better to at least 1 prior anti-myeloma
therapy.
- Participant must have documented disease progression during or after their last
antimyeloma regimen.
Exclusion Criteria
- Participant who has had prior treatment with mezigdomide or carfilzomib.
- Participant has previously received allogeneic stem cell transplant at any time or
received autologous stem cell transplant within 12 weeks of initiating study
treatment.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome:
1. Progression-free Survival (PFS) (Time Frame - Up to approximately 5 years)
Secondary outcome:
1. Recommended Mezigdomide Dose (Time Frame - Up to 12 months):
Stage 1 only
2. Plasma concentrations of Mezigdomide in Combination with Carfilzomib and Dexamethasone (Time Frame - Up to 176 days):
Stage 1 only
3. Overall Survival (OS) (Time Frame - Up to approximately 5 years)
4. Overall Response (OR) (Time Frame - Up to approximately 5 years)
5. Rate Of Very Good Partial Response (VGPR) Or Better (VGPRR) (Time Frame - Up to approximately 5 years):
VGPRR will be calculated as the percentage of participants who achieve best response of VGPR or better according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.
6. Complete Response (CR) Or Better (CRR) (Time Frame - Up to approximately 5 years):
CRR will be calculated as the percentage of participants who achieve best response of CR or better according to the IMWG Uniform Response Criteria for Multiple Myeloma.
7. Time To Response (TTR) (Time Frame - Up to approximately 5 years)
8. Duration Of Response (DOR) (Time Frame - Up to approximately 5 years)
9. Time To Progression (TTP) (Time Frame - Up to approximately 5 years)
10. Time To Next Treatment (TTNT) (Time Frame - Up to approximately 5 years)
11. Progression-free Survival 2 (PFS-2) (Time Frame - Up to approximately 5 years)
12. Minimal Residual Disease (MRD) Negativity Rate (Time Frame - Up to approximately 5 years)
13. Number Of Participants With Adverse Events (AEs) (Time Frame - Up to approximately 5 years)
14. Change From Baseline in the European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) (Time Frame - Up to approximately 5 years):
The EORTC QLQ-C30 is the most commonly used quality of life instrument in oncology trials. The QLQ-C30 consists of 30 questions incorporated into 5 functional domains physical, role, cognitive, emotional, and social), 9 symptom/other scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a single global Quality of Life (QoL)/global health status score. Items in the functional and symptom scale use raw participant response of 1 to 4, where 1 = "not at all" and 4 = "very much." The 2 global items contain responses ranging from 1 "very poor" to 7 "excellent." The recall period is 1 week. All domain scores are transformed in a range from 0 to 100, where a higher functional score indicates more favorable outcomes and a higher score on the symptom domains indicates a less favorable participant outcome. Stage 2 only.
15. Change From Baseline in the European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) (Time Frame - Up to approximately 5 years):
The EORTC QLQ-MY20 is a 20-item myeloma module intended for use among participants varying in disease stage and treatment modality. Participants rate symptoms or problems on a scale from 1 to 4 where 1 = "not at all" and 4 = "very much." Stage 2 only.
- Experimental: MeziKd (Mezigdomide + Carfilzomib + Dexamethasone)
- Active Comparator: Kd (Carfilzomib + Dexamethasone)
- Mezigdomide (BMS-986348 / CC-92480 / ):
Specified dose on specified days - Carfilzomib (Kyprolis):
Specified dose on specified days - Dexamethasone (Decadron / Dex / ):
Specified dose on specified days
Quelle: ClinicalTrials.gov
