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.
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.
Primary outcome:
1. 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))
Secondary outcome:
1. Recommended mezigdomide dose (Time Frame - Up to 12 Months):
Stage 1 only
2. Plasma concentrations of mezigdomide (Time Frame - Up to 134 Days):
Stage 1 only
3. Overall Survival (OS) (Time Frame - From date of randomization to date of death due to any cause (Up to approximately 5 years))
4. 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
5. 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
6. 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
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 (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)
13. Number of participants with Adverse Events (AEs) (Time Frame - Up to approximately 5 years)
14. 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.
15. 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.
- Experimental: MeziVd (mezigdomide, bortezomib and dexamethasone)
- Experimental: PVd (pomalidomide, bortezomib and dexamethasone)
- mezigdomide (BMS-986348 / CC-92480 / ):
Specified dose on specified days - Pomalidomide (Pomalyst / Imnovid / Pom / ):
Specified dose on specified days - Bortezomib (Velcade / BTZ / ):
Specified dose on specified days - Dexamethasone (Decadron / Dex / ):
Specified dose on specified days
Quelle: ClinicalTrials.gov
