A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed or Refractory Multiple Myeloma

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

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Trametinib; Drug: CC-92480; Drug: Dexamethasone; Drug: BMS-986158; Drug: Tazemetostat

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of email MUST contain NCT # and Site #.

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Alberta Health Services AHS - Foothills Medical Centre FMC
      • Contact: Nizar Bahlis, Site 0009; Phone Number: 4039441880
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • University of Alberta - Cross Cancer Institute
      • Contact: Michael Chu, Site 0008; Phone Number: 7804328757
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network UHN - Princess Margaret Hospital PMH
      • Contact: Donna Reece, Site 0004; Phone Number: 4169462824
• Norway
  • Outside US and Canada
    • Oslo, Outside US and Canada, Norway, 0450
      • Recruiting
      • Oslo University Hospital
      • Contact: Fredrik Hellem Schjesvold, Site 0012; Phone Number: +4799697796
• Spain
  • Barcelona, Spain, 08026
    • Recruiting
    • ICO - Hospital Germans Trias I Pujol
    • Contact: Albert Oriol Rocafiguera, Site 0011; Phone Number: 34934978987
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Joaquin Martinez Lopez, Site 0005; Phone Number: 34913908525
  • Santander, Spain, 39008
    • Recruiting
    • Hospital Universitario Marqués de Valdecilla
    • Contact: Enrique Ocio, Site 0003; Phone Number: +34649391848
• United Kingdom
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • NIHR UCLH Clinical Research Facility
    • Contact: Rakesh Popat, Site 0006; Phone Number: 111-111-1111
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Recruiting
      • The Christie NHS Foundation Trust
      • Contact: Emma Searle, Site 0017; Phone Number: 4401614463869
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Withdrawn
      • Local Institution - 0001
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8YA
      • Withdrawn
      • Local Institution - 0014
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Recruiting
      • Churchill Hospital
      • Contact: Karthik Ramasamy, Site 0016; Phone Number: +4401782674844
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • UAB Comprehensive Cancer Center
      • Contact: Luciano Costa, Site 0002; Phone Number: 205-934-9695
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
      • Contact: Syed Abbas Ali, Site 0015; Phone Number: 443-287-7104
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Monique Hartley-Brown, Site 0010; Phone Number: 857-299-5736
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center At Hackensack UMC
      • Contact: David Siegel, Site 0013; Phone Number: 551-996-8704
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Saad Usmani, Site 0007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Arm A: Dose Finding	Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days; Drug: Tazemetostat; Specified dose on specified days
Experimental: Part 1 Arm B: Dose Finding	Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days; Drug: BMS-986158; Specified dose on specified days
Experimental: Part 1 Arm C: Dose Finding	Drug: Trametinib; Specified dose on specified days; Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days
Active Comparator: Part 2 Arm D: Dose Expansion	Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days
Experimental: Part 2 Arm E: Dose Expansion	Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days; Drug: Tazemetostat; Specified dose on specified days
Experimental: Part 2 Arm G: Dose Expansion	Drug: Trametinib; Specified dose on specified days; Drug: CC-92480; Specified dose on specified days; Other Names: BMS-986348; Drug: Dexamethasone; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome 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
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
Number of participants with AEs leading to discontinuation	Up to approximately 4 years
Number of deaths	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

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response (DOR)	Up to approximately 4 years
Progression-free survival (PFS)	Up to approximately 4 years
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): October 12, 2026

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 12, 2022

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Trametinib; Dexamethasone; CC-92480; Tazemetostat; BMS-986348; BMS-986158
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; trametinib; tazemetostat
• Other Study ID Numbers: CA057-003; U1111-1269-5704 (Registry Identifier: WHO); 2023-509384-25 (Other Identifier: EU CTR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No