Clinical trial NCT05372354: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: BMS-986348
CC-92480
BMS-986158
Dexamethasone
Tazemetostat
Trametinib
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-05-12
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 at least 2 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From first participant first visit until 28 days after the last participant discontinues study treatment, up to approximately 4 years
measure: Establish recommended Phase 2 dose (RP2D)
timeFrame: Up to approximately 2 years
measure: Establish dosing schedule of each combination for Part 2 Dose Expansion
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to approximately 4 years
measure: Very good partial response rate (VGPRR)
timeFrame: Up to approximately 4 years
measure: Complete response rate (CRR)
timeFrame: Up to approximately 4 years
measure: Time-to-response (TTR)
timeFrame: Up to approximately 4 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 4 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 4 years
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to approximately 28 days
measure: Time to maximum plasma concentration (Tmax)
timeFrame: Up to approximately 28 days
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to approximately 28 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Calgary
country: Canada
facility: Alberta Health Services AHS - Foothills Medical Centre FMC
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta - Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network UHN - Princess Margaret Hospital PMH
state: Ontario
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barcelona
country: Spain
facility: ICO - Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Leicester
country: United Kingdom
facility: Local Institution - 0001
state: Leicestershire
city: Liverpool
country: United Kingdom
facility: Local Institution - 0014
state: Merseyside
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
city: London
country: United Kingdom
facility: NIHR UCLH Clinical Research Facility
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: