Multiple Myeloma
Conditions
Keywords
BMS-986348, CC-92480, BMS-986158, Dexamethasone, Tazemetostat, Trametinib
Brief summary
The purpose of this study is to assess the safety, tolerability and preliminary effectiveness of CC-92480 (BMS-986348) in novel therapeutic combinations for the treatment of Relapsed or Refractory Multiple Myeloma (RRMM).
Interventions
DRUGCC-92480
Specified dose on specified days
DRUGTazemetostat
Specified dose on specified days
DRUGBMS-986158
Specified dose on specified days
DRUGTrametinib
Specified dose on specified days
DRUGDexamethasone
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory multiple myeloma (MM) and must: 1. Have documented disease progression during or after their last myeloma therapy. 2. For Part 1 Dose Finding: Be refractory to, intolerant to, or not a candidate for available, established therapies known to provide clinical benefit in MM; For Part 2 Dose Expansion: Be refractory to or have relapsed after the protocol specified number of prior lines of therapy that include an immunomodulatory drug (IMiD), a proteasome inhibitor, an anti-CD38 mAb, and a T-cell redirecting therapy (TRT, eg, a CAR-T or T-cell engaging bispecific treatment) unless the participant is not a candidate for TRT. * Must have measurable disease. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. * Agree to follow the CC-92480 Pregnancy Prevention Plan (PPP).
Exclusion criteria
* Known active or history of central nervous system (CNS) involvement of MM * Plasma cell leukemia; Waldenstrom's macroglobulinemia; polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome; or clinically significant light-chain amyloidosis. * Impaired cardiac function or clinically significant cardiac disease * Previous SARS-CoV-2 infection within 14 days for asymptomatic or mild symptomatic infections or 28 days for severe/critical illness prior to Cycle 1 Day 1 (C1D1) * For Part 1: received prior therapy with CC-92480 * For Part 2: received prior therapy with CC-92480, tazemetostat, BMS-986158, or trametinib * Previously received allogeneic stem-cell transplant at any time or received autologous stem-cell transplant within 12 weeks of initiating study treatment * Received any of the following within 14 days prior to initiating study treatment: 1. Plasmapheresis 2. Major surgery 3. Radiation therapy other than local therapy for myeloma associated bone lesions 4. Use of any systemic anti-myeloma drug therapy * Used any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to initiating study treatment * COVID-19 vaccine within 14 days prior to C1D1 Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events (AEs) | From first participant first visit until 28 days after the last participant discontinues study treatment, up to approximately 4 years |
| Number of participants with Serious AEs | Up to approximately 4 years |
| Number of participants with AEs meeting protocol-defined DLT criteria | Up to approximately 4 years |
| Number of participants with AEs leading to discontinuation | Up to approximately 4 years |
| Number of deaths | Up to approximately 4 years |
| Establish recommended Phase 2 dose (RP2D) | Up to approximately 2 years |
| Establish dosing schedule of each combination for Part 2 Dose Expansion | Up to approximately 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Time to maximum plasma concentration (Tmax) | Up to approximately 28 days |
| Area under the concentration-time curve (AUC) | Up to approximately 28 days |
| Overall response rate (ORR) | Up to approximately 4 years |
| Apparent total body clearance (CLT/F) | Up to approximately 28 days |
| Apparent volume of distribution (Vz/F) | Up to approximately 28 days |
| Terminal Half-Life (T-Half) | Up to approximately 28 days |
| Very good partial response rate (VGPRR) | Up to approximately 4 years |
| Complete response rate (CRR) | Up to approximately 4 years |
| Time-to-response (TTR) | Up to approximately 4 years |
| Duration of response (DOR) | Up to approximately 4 years |
| Progression-free survival (PFS) | Up to approximately 4 years |
| Maximum observed plasma concentration (Cmax) | Up to approximately 28 days |
Countries
Canada, Norway, Spain, United Kingdom, United States
Contacts
Primary ContactBMS Study Connect Contact Center www.BMSStudyConnect.com
Backup ContactFirst line of email MUST contain NCT # and Site #.
Outcome results
None listed