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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: CC-92480
* Drug: Tazemetostat
* Drug: BMS-986158
* Drug: Trametinib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMS-986348, CC-92480, BMS-986158, Dexamethasone, Tazemetostat, Trametinib