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

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 WHOClassification

• R/R myelodysplastic syndromes (MDS) as defined by the 2016 WHO Classification withintermediate, high or very high risk by Revised International Prognostic ScoringSystem (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 asdisseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolleddisseminated 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 ≤ 5half-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 oflaboratory abnormalities, which places the participant at unacceptable risk ifhe/she were to participate in the study

• Pregnant or nursing participants.

Other protocol-defined inclusion/exclusion criteria apply