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

Bristol-Myers Squibb (BMS)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Trametinib; Drug: Dexamethasone; Drug: BMS-986158; Drug: CC-92480; Drug: Tazemetostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT05372354

CA057-003

U1111-1269-5704 (Registry Identifier)

2021-005167-51 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Relapsed or refractory multiple myeloma (MM) and must:

  1. have documented disease progression during or after their last myeloma therapy
  2. be refractory to, intolerant to, or not a candidate for available, established therapies known to provide clinical benefit in MM

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 7 patient groups

Part 1 Arm A: Dose Finding

Experimental group

Treatment:

Drug: Tazemetostat

Drug: Dexamethasone

Drug: CC-92480

Part 1 Arm B: Dose Finding

Experimental group

Treatment:

Drug: Dexamethasone

Drug: BMS-986158

Drug: CC-92480

Part 1 Arm C: Dose Finding

Experimental group

Treatment:

Drug: Dexamethasone

Drug: CC-92480

Drug: Trametinib

Part 2 Arm D: Dose Expansion

Active Comparator group

Treatment:

Drug: Dexamethasone

Drug: CC-92480

Part 2 Arm E: Dose Expansion

Experimental group

Treatment:

Drug: Tazemetostat

Drug: Dexamethasone

Drug: CC-92480

Part 2 Arm F: Dose Expansion

Experimental group

Treatment:

Drug: Dexamethasone

Drug: BMS-986158

Drug: CC-92480

Part 2 Arm G: Dose Expansion

Experimental group

Treatment:

Drug: Dexamethasone

Drug: CC-92480

Drug: Trametinib