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

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05372354

Collaborator

(none)

220

Enrollment

Location

Arms

33.1

Anticipated Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: CC-92480 Drug: Tazemetostat Drug: BMS-986158 Drug: Trametinib Drug: Dexamethasone	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Apr 4, 2025

Anticipated Study Completion Date :

Apr 4, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Arm A: Dose Finding	Drug: CC-92480 Specified dose on specified days Other Names: BMS-986348 Drug: Tazemetostat Specified dose on specified days Drug: Dexamethasone 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: BMS-986158 Specified dose on specified days Drug: Dexamethasone Specified dose on specified days
Experimental: Part 1 Arm C: Dose Finding	Drug: CC-92480 Specified dose on specified days Other Names: BMS-986348 Drug: Trametinib Specified dose on specified days 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: Tazemetostat Specified dose on specified days Drug: Dexamethasone Specified dose on specified days
Experimental: Part 2 Arm F: Dose Expansion	Drug: CC-92480 Specified dose on specified days Other Names: BMS-986348 Drug: BMS-986158 Specified dose on specified days Drug: Dexamethasone Specified dose on specified days
Experimental: Part 2 Arm G: Dose Expansion	Drug: CC-92480 Specified dose on specified days Other Names: BMS-986348 Drug: Trametinib Specified dose on specified days Drug: Dexamethasone Specified dose on specified days

Outcome Measures

Primary Outcome Measures

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]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Relapsed or refractory multiple myeloma (MM) and must:

have documented disease progression during or after their last myeloma therapy
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:

Plasmapheresis
Major surgery
Radiation therapy other than local therapy for myeloma associated bone lesions
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