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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05372354Sponsor: Bristol-Myers SquibbLast updated: 2025-09-05

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).

Arms & 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

Outcome measures

Primary

  • 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

  • Overall response rate (ORR)

    Time frame: Up to approximately 4 years

  • Very good partial response rate (VGPRR)

    Time frame: Up to approximately 4 years

  • Complete response rate (CRR)

    Time frame: Up to approximately 4 years

  • Time-to-response (TTR)

    Time frame: Up to approximately 4 years

  • Duration of response (DOR)

    Time frame: Up to approximately 4 years

  • Progression-free survival (PFS)

    Time frame: Up to approximately 4 years

  • Maximum observed plasma concentration (Cmax)

    Time frame: Up to approximately 28 days

  • Time to maximum plasma concentration (Tmax)

    Time frame: Up to approximately 28 days

  • Area under the concentration-time curve (AUC)

    Time frame: Up to approximately 28 days

  • Terminal Half-Life (T-Half)

    Time frame: Up to approximately 28 days

  • Apparent total body clearance (CLT/F)

    Time frame: Up to approximately 28 days

  • Apparent volume of distribution (Vz/F)

    Time frame: Up to approximately 28 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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/exclusion criteria apply

Study locations (5)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35249

Recruiting
Luciano Costa, Site 0002 · Contact

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287

Recruiting
Syed Abbas Ali, Site 0015 · Contact

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Monique Hartley-Brown, Site 0010 · Contact

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, 07601

Recruiting
David Siegel, Site 0013 · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

Recruiting
Saad Usmani, Site 0007 · Contact