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) (SUCCESSOR-2)

• ClinicalTrials.gov Identifier: NCT05552976
• Recruitment Status: Recruiting
• First Posted: September 23, 2022
• Last Update Posted: May 2, 2024
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: September 21, 2022
• First Posted Date: September 23, 2022
• Last Update Posted Date: May 2, 2024
• Actual Study Start Date: January 10, 2023
• Estimated Primary Completion Date: February 4, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 21, 2022): Progression-free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 13, 2023)

• Recommended Mezigdomide Dose [ Time Frame: Up to 12 months ]
  Stage 1 only
• Plasma concentrations of Mezigdomide in Combination with Carfilzomib and Dexamethasone [ Time Frame: Up to 176 days ]
  Stage 1 only
• Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
• Overall Response (OR) [ Time Frame: Up to approximately 5 years ]
• 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.
• 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.
• 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 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.
• 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.

Original Secondary Outcome Measures (submitted: September 21, 2022)

• Recommended CC-92480 Dose [ Time Frame: Up to 12 months ]
  Stage 1 only
• Plasma concentrations of CC-92480 in Combination with Carfilzomib and Dexamethasone [ Time Frame: Up to 176 days ]
  Stage 1 only
• Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
• Overall Response Rate (ORR) [ Time Frame: Up to approximately 5 years ]
• 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.
• Rate Of 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.
• 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 ]
• Mean 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.
• Mean 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.

• 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 in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (SUCCESSOR-2)
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a two-stage inferentially seamless design.

Masking: None (Open Label)
Masking Description:

This is an open-label study; however, any review of aggregate study data by the Sponsor will be performed in a blinded manner.

Primary Purpose: Treatment

• Condition: Relapsed or Refractory Multiple Myeloma

Intervention

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

  • BMS-986348
  • CC-92480
• Drug: Carfilzomib
  Specified dose on specified days
  Other Name: Kyprolis
• Drug: Dexamethasone
  Specified dose on specified days
  Other Names:

  • Decadron
  • Dex

Study Arms

• Experimental: MeziKd (Mezigdomide + Carfilzomib + Dexamethasone)
  Interventions:

  • Drug: Mezigdomide
  • Drug: Carfilzomib
  • Drug: Dexamethasone
• Active Comparator: Kd (Carfilzomib + Dexamethasone)
  Interventions:

  • Drug: Carfilzomib
  • Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 21, 2022): 525
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 25, 2029
• Estimated Primary Completion Date: February 4, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

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

• Listed Location Countries: Argentina, Australia, Austria, Brazil, Bulgaria, Canada, China, Colombia, Denmark, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Puerto Rico, Romania, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05552976
• Other Study ID Numbers: CA057-008
• 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: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: May 2024