A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of mezigdomide (CC-92480), bortezomib and dexamethasone (MeziVd) versus pomalidomide, bortezomib and dexamethasone (PVd) in participants with relapsed or refractory multiple myeloma (RRMM) who received between 1 to 3 prior lines of therapy and who have had prior lenalidomide exposure.

Official Title
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A Phase 3, Two-Stage, Randomized, Multicenter, Open-Label Study Comparing Mezigdomide (CC-92480), Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Subjects With Relapsed or Refractory Multiple Myeloma (RRMM): SUCCESSOR-1

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: mezigdomide
* Drug: Pomalidomide
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has documented diagnosis of MM and measurable disease, defined as any of the following: M-protein ≥ 0.5 grams per deciliter (g/dL) by serum protein electrophoresis (sPEP) or M-protein ≥ 200 milligrams (mg) per 24-hour urine collection by urine protein electrophoresis (uPEP) For participants without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio. Participants received 1 to 3 prior lines of antimyeloma therapy. Participants achieved minimal response [MR] or better to at least 1 prior antimyeloma therapy. Exclusion Criteria: Participant has had progression during treatment or within 60 days of the last dose of a proteasome inhibitor, except as noted below: a. Subjects who progressed while being treated with, or within 60 days of last dose of bortezomib maintenance given once every 2 weeks or less are not excluded. For participants with prior treatment of a bortezomib containing regimen, the best response achieved was not a minimal response (MR) or better, or participant discontinued bortezomib due to toxicity. Participant has had prior treatment with mezigdomide or pomalidomide. Other 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MeziVd (mezigdomide, bortezomib and dexamethasone)<br> | Drug: mezigdomide<br>* Specified dose on specified days<br>* Other names: CC-92480;Drug: Bortezomib<br>* Specified dose on specified days<br>* Other names: BTZ;Drug: Dexamethasone<br>* Specified dose on specified days<br>* Other names: Dex;|
| Experimental: PVd (pomalidomide, bortezomib and dexamethasone)<br> | Drug: Pomalidomide<br>* Specified dose on specified days<br>* Other names: Pom;Drug: Bortezomib<br>* Specified dose on specified days<br>* Other names: BTZ;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) |  | From date of randomization to date of disease progression or death due to any cause (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 | Stage 1 only | Up to 134 Days | 
| Overall Survival (OS) |  | From date of randomization to date of death due to any cause (Up to approximately 5 years) | 
| Overall Response (OR) | OR is defined as the number of participants who achieve best response of partial response (PR) or better according to the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma | Up to approximately 5 years | 
| Complete Response (CR) or better | Defined as the number of participants who achieve best response of complete response (CR) or better according to the IMWG Uniform Response Criteria for Multiple Myeloma | Up to approximately 5 Years | 
| Very Good Partial Response (VGPR) or better | Defined as the number of participants who achieve best response of very good partial response (VGPR) 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 | Defined as the number of participants who achieve complete response (CR) or better and MRD negative (defined at a sensitivity of a minimum of 1 in 105 nucleated cells) | Up to approximately 5 years | 
| Number of participants with Adverse Events (AEs) |  | Up to approximately 5 years | 
| Change from baseline in European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) scores | 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 European Organization for Research and Treatment of Cancer - Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) score | 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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Multiple myeloma, RRMM, MeziVd, PVd, CC92480, pomalidomide, bortezomib, dexamethasone, mezigdomide