A Study to Assess the Effect of CC-95251 in Participants With Acute Myeloid Leukemia and Myelodysplastic Syndromes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and preliminary clinical activity of CC-95251 alone and in combination with antineoplastic agents in participants with relapsed or refractory acute myeloid leukemia and relapsed or refractory and treatment-naive higher risk melodysplastic syndromes.

Official Title
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A Phase 1, Open-label, Dose Finding Study of CC-95251 Alone and in Combination With Antineoplastic Agents in Subjects With Acute Myeloid Leukemia and Myelodysplastic Syndromes

Conditions
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Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: CC-95251
* Drug: Azacitidine
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Eastern Cooperative Oncology Group Performance Status of 0 to 2 For Parts A & B: Relapsed or refractory (R/R) acute myeloid leukemia (AML) as defined by the 2016 WHO Classification R/R myelodysplastic syndromes (MDS) as defined by the 2016 WHO Classification with intermediate, high or very high risk by Revised International Prognostic Scoring System (IPSS-R) For Part C: • Treatment-naïve (TN) (ie, previously untreated) MDS as defined by the 2016 WHO Classification with intermediate, high or very high risk by IPSS-R For Part D: • TN AML as defined by the 2016 WHO Classification, including secondary AML and therapy-related AML in participants who are ineligible (IE) for intensive chemotherapy (IC) and allogeneic hematopoietic stem cell transplant (HSCT) Exclusion Criteria: Acute promyelocytic leukemia Immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation Participants who have received prior treatment with a CD47 or SIRPα targeting agent Participant is on chronic systemic immunosuppressive therapy or corticosteroids Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting study treatment, whichever is shorter (relapsed or refractory participants only). Any condition including, active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study Pregnant or nursing participants. 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: CC-95251 monotherapy<br> | Drug: CC-95251<br>* Specified dose on specified days<br>* Other names: BMS-986351;|
| Experimental: CC-95251 + azacitidine<br> | Drug: CC-95251<br>* Specified dose on specified days<br>* Other names: BMS-986351;Drug: Azacitidine<br>* Specified dose on specified days<br>|
| Experimental: CC-95251 + azacitidine + venetoclax<br> | Drug: Venetoclax<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 a Dose-limiting toxicity (DLT) |  | Up to 42 days | 
| Incidence of adverse events (AEs) |  | Up to 56 days after the last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate (CRR) for acute myeloid leukemia (AML) according to the modified European Leukemia Net (ELN) response criteria |  | Up to 2 years after end of treatment | 
| Overall response rate (ORR) for AML |  | Up to 2 years after end of treatment | 
| CRR for myelodysplastic syndromes (MDS) according to the modified International Working Group (IWG) Response Criteria |  | Up to 2 years after end of treatment | 
| ORR for MDS |  | Up to 2 years after end of treatment | 
| Duration of remission |  | Up to 2 years after end of treatment | 
| Duration of response |  | Up to 2 years after end of treatment | 
| Stable disease rate is the rate of MDS participants whose best response is stable disease |  | Up to 2 years after end of treatment | 
| Relapse-free survival |  | Up to 2 years after end of treatment | 
| Event-free survival |  | Up to 2 years after end of treatment | 
| Progression-free survival |  | Up to 2 years after end of treatment | 
| Time to remission/response |  | Up to 2 years after end of treatment | 
| Transfusion independence |  | Up to 2 years after end of treatment | 
| Time to AML transformation for MDS participants |  | Up to 2 years after end of treatment | 
| Overall survival (OS) rates at 6 months |  | Up to 2 years after end of treatment | 
| OS rates at 12 months |  | Up to 2 years after end of treatment | 
| Maximum plasma concentration of drug (Cmax) |  | Up to 8 weeks post-dose of CC-95251 | 
| Minimum serum concentration (Cmin) |  | Up to 8 weeks post-dose of CC-95251 | 
| Trough observed serum concentration (Ctrough) |  | Up to 8 weeks post-dose of CC-95251 | 
| Presence of anti-CC-95251 antibodies (ADAs) using a validated electrochemiluminescence (ECL) assay |  | Up to 8 weeks post-dose of CC-95251 | 
| Frequency of ADAs using a validated ECL assay |  | Up to 8 weeks post-dose of CC-95251 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-95251, MDS, Myelodysplastic Syndromes, Acute Myeloid Leukemia, AML, Hematologic Cancers, Leukemia, Anti-SIRPa antibody