A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (SUCCESSOR-2)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Two-stage, Randomized, Multicenter, Open-label Study Comparing Mezigdomide (CC-92480/BMS-986348), Carfilzomib, and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM): SUCCESSOR-2

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Mezigdomide
* Drug: Carfilzomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has documented diagnosis of multiple myeloma and measurable disease, defined as any of the following: Myeloma-protein (M-protein) ≥ 0.5 grams/deciliter (g/dL) by serum protein electrophoresis (sPEP), or M-protein ≥ 200 milligrams (mg)/24-hour urine collection by urine protein electrophoresis (uPEP) or, 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. Additional protocol-defined criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two-stage inferentially seamless design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MeziKd (Mezigdomide + Carfilzomib + Dexamethasone)<br> | Drug: Mezigdomide<br>* Specified dose on specified days<br>* Other names: CC-92480;Drug: Carfilzomib<br>* Specified dose on specified days<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Specified dose on specified days<br>* Other names: Dex;|
| Active Comparator: Kd (Carfilzomib + Dexamethasone)<br> | Drug: Carfilzomib<br>* Specified dose on specified days<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Specified dose on specified days<br>* Other names: Dex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) |  | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Mezigdomide Dose | Stage 1 only | Up to 12 months | 
| Plasma concentrations of Mezigdomide in Combination with Carfilzomib and Dexamethasone | Stage 1 only | Up to 176 days | 
| Overall Survival (OS) |  | Up to approximately 5 years | 
| Overall Response (OR) |  | Up to approximately 5 years | 
| Rate Of Very Good Partial Response (VGPR) Or Better (VGPRR) | 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. | Up to approximately 5 years | 
| Complete Response (CR) Or Better (CRR) | 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. | Up to approximately 5 years | 
| Time To Response (TTR) |  | Up to approximately 5 years | 
| Duration Of Response (DOR) |  | Up to approximately 5 years | 
| Time To Progression (TTP) |  | Up to approximately 5 years | 
| Time To Next Treatment (TTNT) |  | Up to approximately 5 years | 
| Progression-free Survival 2 (PFS-2) |  | Up to approximately 5 years | 
| Minimal Residual Disease (MRD) Negativity Rate |  | Up to approximately 5 years | 
| Number Of Participants With Adverse Events (AEs) |  | Up to approximately 5 years | 
| Change From Baseline in the European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) | 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. | Up to approximately 5 years | 
| Change From Baseline in the European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) | 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. | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-92480, BMS-986348, Carfilzomib, Dexamethasone, Multiple Myeloma, Mezigdomide