A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (SUCCESSOR-1)

• ClinicalTrials.gov Identifier: NCT05519085
• Recruitment Status: Recruiting
• First Posted: August 29, 2022
• Last Update Posted: May 14, 2024
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: August 25, 2022
• First Posted Date: August 29, 2022
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: September 20, 2022
• Estimated Primary Completion Date: November 3, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 25, 2022): Progression-free Survival (PFS) [ Time Frame: From date of randomization to date of disease progression or death due to any cause (Up to approximately 5 years) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 25, 2023)

• Recommended mezigdomide dose [ Time Frame: Up to 12 Months ]
  Stage 1 only
• Plasma concentrations of mezigdomide [ Time Frame: Up to 134 Days ]
  Stage 1 only
• Overall Survival (OS) [ Time Frame: From date of randomization to date of death due to any cause (Up to approximately 5 years) ]
• Overall Response (OR) [ Time Frame: Up to approximately 5 years ]
  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
• Complete Response (CR) or better [ Time Frame: Up to approximately 5 Years ]
  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
• Very Good Partial Response (VGPR) or better [ Time Frame: Up to approximately 5 years ]
  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
• Time to Response (TTR) [ Time Frame: Up to approximately 5 years ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 5 years ]
• Time to Progression (TTP) [ Time Frame: Up to approximately 5 years ]
• Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 5 years ]
• Progression-free Survival 2 (PFS-2) [ Time Frame: Up to approximately 5 years ]
• Minimal Residual Disease (MRD) negativity [ Time Frame: Up to approximately 5 years ]
  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)
• Number of participants with Adverse Events (AEs) [ Time Frame: 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 [ 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.
• Change from baseline in European Organization for Research and Treatment of Cancer - Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) score [ 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.

Original Secondary Outcome Measures (submitted: August 25, 2022)

• Recommended CC- 92480 dose [ Time Frame: Up to 12 Months ]
  Stage 1 only
• Plasma concentrations of CC-92480 [ Time Frame: Up to 134 Days ]
  Stage 1 only
• Overall Survival (OS) [ Time Frame: From date of randomization to date of death due to any cause (Up to approximately 5 years) ]
• Overall Response Rate (ORR) [ Time Frame: Up to approximately 5 years ]
• Percentage of participants with Complete Response Rate (CRR) or better as assessed by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma [ Time Frame: Up to approximately 5 Years ]
• Percentage of participants with Very Good Partial Response Rate (VGPRR) or better as assessed by the IMWG Uniform Response Criteria for Multiple Myeloma [ Time Frame: Up to approximately 5 years ]
• Time to Response (TTR) [ Time Frame: Up to approximately 5 years ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 5 years ]
• Time to Progression (TTP) [ Time Frame: Up to approximately 5 years ]
• Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 5 years ]
• Progression-free Survival 2 (PFS-2) [ Time Frame: Up to approximately 5 years ]
• Minimal Residual Disease (MRD) negativity rate [ Time Frame: Up to approximately 5 years ]
• Number of participants with Adverse Events (AEs) [ Time Frame: 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 [ 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.
• Change from baseline in European Organization for Research and Treatment of Cancer - Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) score [ 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed or Refractory Multiple Myeloma

Intervention

• Drug: mezigdomide
  Specified dose on specified days
  Other Names:

  • BMS-986348
  • CC-92480
• Drug: Pomalidomide
  Specified dose on specified days
  Other Names:

  • Pomalyst
  • Imnovid
  • Pom
• Drug: Bortezomib
  Specified dose on specified days
  Other Names:

  • Velcade
  • BTZ
• Drug: Dexamethasone
  Specified dose on specified days
  Other Names:

  • Decadron
  • Dex

Study Arms

• Experimental: MeziVd (mezigdomide, bortezomib and dexamethasone)
  Interventions:

  • Drug: mezigdomide
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: PVd (pomalidomide, bortezomib and dexamethasone)
  Interventions:

  • Drug: Pomalidomide
  • Drug: Bortezomib
  • Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 25, 2023): 810
• Original Estimated Enrollment (submitted: August 25, 2022): 760
• Estimated Study Completion Date: November 30, 2033
• Estimated Primary Completion Date: November 3, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

- Participant has documented diagnosis of MM and measurable disease, defined as any of the following:.

i) M-protein ≥ 0.5 grams per deciliter (g/dL) by serum protein electrophoresis (sPEP) or.

ii) M-protein ≥ 200 milligrams (mg) per 24-hour urine collection by urine protein electrophoresis (uPEP).

iii) 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:.

  i) 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 Inclusion/Exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com; 855-907-3286; Clinical.Trials@bms.com

Contact: First line of the email MUST contain the NCT# and Site #.

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Portugal, Puerto Rico, Romania, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05519085
• Other Study ID Numbers: CA057-001; 2021-001957-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.html
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: See Plan Description
• Access Criteria: See Plan Description
• URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

• Current Responsible Party: Celgene
• Original Responsible Party: Bristol-Myers Squibb
• Current Study Sponsor: Celgene
• Original Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: May 2024