An Exploratory Phase 1b/2a Multicenter, Open-Label, Novel-Novel Combination Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CC-92480 (BMS-986348) in Novel Therapeutic Combinations in Participants With Relapsed or Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- CC-92480
- Conditions
- Multiple Myeloma
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 260
- Locations
- 17
- Primary Endpoint
- Number of participants with adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Relapsed or refractory multiple myeloma (MM) and must:
- •Have documented disease progression during or after their last myeloma therapy.
- •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
- •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:
- •Plasmapheresis
- •Major surgery
Arms & Interventions
Part 1 Arm A: Dose Finding
Intervention: CC-92480
Part 1 Arm A: Dose Finding
Intervention: Tazemetostat
Part 1 Arm A: Dose Finding
Intervention: Dexamethasone
Part 1 Arm B: Dose Finding
Intervention: CC-92480
Part 1 Arm B: Dose Finding
Intervention: BMS-986158
Part 1 Arm B: Dose Finding
Intervention: Dexamethasone
Part 1 Arm C: Dose Finding
Intervention: CC-92480
Part 1 Arm C: Dose Finding
Intervention: Trametinib
Part 1 Arm C: Dose Finding
Intervention: Dexamethasone
Part 2 Arm D: Dose Expansion
Intervention: CC-92480
Part 2 Arm D: Dose Expansion
Intervention: Dexamethasone
Part 2 Arm E: Dose Expansion
Intervention: CC-92480
Part 2 Arm E: Dose Expansion
Intervention: Tazemetostat
Part 2 Arm E: Dose Expansion
Intervention: Dexamethasone
Part 2 Arm G: Dose Expansion
Intervention: CC-92480
Part 2 Arm G: Dose Expansion
Intervention: Trametinib
Part 2 Arm G: Dose Expansion
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs)
Time Frame: 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
Time Frame: Up to approximately 4 years
Number of participants with AEs meeting protocol-defined DLT criteria
Time Frame: Up to approximately 4 years
Number of participants with AEs leading to discontinuation
Time Frame: Up to approximately 4 years
Number of deaths
Time Frame: Up to approximately 4 years
Establish recommended Phase 2 dose (RP2D)
Time Frame: Up to approximately 2 years
Establish dosing schedule of each combination for Part 2 Dose Expansion
Time Frame: Up to approximately 2 years
Secondary Outcomes
- Overall response rate (ORR)(Up to approximately 4 years)
- 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)
- Time to maximum plasma concentration (Tmax)(Up to approximately 28 days)
- Area under the concentration-time curve (AUC)(Up to approximately 28 days)
- Terminal Half-Life (T-Half)(Up to approximately 28 days)
- Apparent total body clearance (CLT/F)(Up to approximately 28 days)
- Apparent volume of distribution (Vz/F)(Up to approximately 28 days)