Detailed Description:
This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing
the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab
(IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with
relapsed or refractory multiple myeloma (RRMM). Approximately 200 patients randomized in
stage 1 to one of three iberdomide dose levels of 1, 1.3, or 1.6 mg in combination with
daratumumab and dexamethasone (Treatment Arms A1, A2, or A3), or to the DVd comparator arm
(Treatment Arm B).
In Stage 2 of the study, approximately 664 additional subjects will be randomized 1:1 between
2 treatment arms:
- Approximately 332 subjects will be randomized to receive Treatment Arm A (IberDd)
- Approximately 332 subjects will be randomized to receive Treatment Arm B (DVd)
Participants in both treatment arms will continue to receive treatment until confirmed
progressive disease (PD), unacceptable toxicity or withdrawal of consent. To ensure accuracy
and completeness of the primary endpoint assessment of progression-free survival (PFS),
participants who permanently discontinue study treatment for any reason, other than confirmed
PD or withdrawal of consent, will continue to be followed for disease assessment.
The study will be conducted in compliance with International Council for Harmonisation (ICH)
and Good Clinical Practices (GCPs).
Inclusion Criteria
- Documented diagnosis of multiple myeloma (MM) and measurable disease.
- Received 1 to 2 prior lines of anti-myeloma therapy.
- Must have documented disease progression during or after their last anti-myeloma
regimen.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
Exclusion Criteria
- Any condition that confounds the ability to interpret data from the study.
- Has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),
or clinically significant amyloidosis.
- Known central nervous system involvement with MM.
- Prior therapy with iberdomide.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome:
1. Progression-free Survival (PFS) (Time Frame - Up to approximately 5 years):
To compare the efficacy of iberdomide, daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in terms of progression-free survival (PFS) in participants with relapsed or refractory multiple myeloma (RRMM).
Secondary outcome:
1. Overall Survival (OS) (Time Frame - Up to approximately 5 years):
To evaluate clinical efficacy in terms of overall survival (OS) in participants with relapsed or refractory multiple myeloma (RRMM) treated with iberdomide, daratumumab, and dexamethasone (IberDd) compared to daratumumab, bortezomib, and dexamethasone (DVd).
2. Minimal Residual Disease (MRD) negativity rate (Time Frame - Up to approximately 5 years):
Proportion of participants who achieve complete response (CR) or better and are MRD negative (defined at a sensitivity of a minimum of 1 in 105 nucleated cells by next generation flow cytometry).
3. Overall Response Rate (ORR) (Time Frame - Up to approximately 5 years):
Calculated as percentage of participants who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for multiple myeloma.
4. Time to response (TTR) (Time Frame - Up to approximately 5 years):
Time from randomization to the first documentation of response (PR or better).
5. Duration of Response (DoR) (Time Frame - Up to approximately 5 years):
Time from the first documentation of response (PR or better) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
6. Time to Progression (TTP) (Time Frame - Up to approximately 5 years):
The time from randomization to the first documented disease progression.
7. Time to Next Treatment (TTNT) (Time Frame - Up to approximately 5 years):
Time from randomization to the start of the next antimyeloma treatment.
8. Progression-free Survival 2 (PFS2) (Time Frame - Up to approximately 5 years):
Time from randomization to progression on the next anti-myeloma treatment or death due to any cause, whichever occurs first.
9. Safety (Time Frame - Up to approximately 5 years):
Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment.
10. European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) (Time Frame - Up to approximately 5 years):
Mean changes from baseline in subscale scores in subject-reported health related quality of life outcomes and multiple myeloma-related symptoms as measured by the EORTC QLQ-C30.
11. European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) (Time Frame - Up to approximately 5 years):
EORTC QLQ-MY20 is a 20-item myeloma module intended for use among participants varying in disease stage and treatment modality. Mean changes from baseline in subscale scores in subject-reported health related quality of life outcomes and multiple myeloma-related symptoms as measured by the EORTC QLQ- MY20.
12. Recommended iberdomide dose for Stage 2 (Time Frame - Up to approximately 1 year)
13. Area under the plasma concentration-time curve from time zero to tau (AUC(TAU)) (Time Frame - Up to approximately 1 year)
14. Maximum plasma concentration (Cmax) (Time Frame - Up to approximately 1 year)
15. Time to maximum plasma concentration (Tmax) (Time Frame - Up to approximately 1 year)
- Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 1
Participants will receive oral iberdomide, subcutaneous daratumumab and oral dexamethasone. - Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 2
- Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 3
- Active Comparator: Daratumumab in combination with dexamethasone and bortezomib
Participants will receive subcutaneous daratumumab, bortezomib and oral dexamethasone
- Dexamethasone:
Oral dexamethasone 40mg on days 1, 8, 15, 22 of a 28-day cycle - Daratumumab (DARZALEX FASPRO):
Subcutaneous Daratumumab 1800mg on Days 1, 8, 15 and 22 for Cycles 1 to 2, on Days 1 and 15 for Cycles 3 to 6, and then on Day 1 for Cycle 7 of a 28-day cycle - Bortezomib:
Subcutaneous Bortezomib 1.3 mg/m2 on Days 1, 4, 8 and 11 of each 21-day cycle for a total of 8 cycles. - Iberdomide (CC-220 / BMS-986382 / ):
Oral Iberdomide 1.0mg on Days 1 to 21 of a 28-day cycle - Iberdomide (CC-220 / BMS-986382 / ):
Oral Iberdomide 1.3mg on Days 1 to 21 of a 28-day cycle - Iberdomide (CC-220 / BMS-986382 / ):
Oral Iberdomide 1.6mg on Days 1 to 21 of a 28-day cycle
Quelle: ClinicalTrials.gov
