A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies

Part A Inclusion Criteria

• Participants with cytologically/histologically confirmed MDS (2016 World Health Organization (WHO) classification) with

• Measurable disease per WHO MDS with excess blasts criteria

• MDS that is relapsed or refractory and must not have other therapeutic options

• Treatment failure after prior hypomethylating agent (HMA) therapy for MDS

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Part B Inclusion Criteria

• Participants with cytologically/histologically confirmed MDS (WHO classification) with:

• Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria

• MDS that is relapsed or refractory and must not have other therapeutic options

• Treatment failure after prior HMA therapy for MDS

• ECOG Performance Status of 0-2

Part C Inclusion Criteria

• Participants with relapsed or refractory AML (ICC 2022) (except for acute promyelocytic leukemia [APL]):

• Who have received either 2 or 3 previous regimens

• Who have received 1 previous regimen to treat active disease and have at least one of the following:

• Age > 60 and ≤75 years.

• Primary resistant AML or secondary AML

• First CR duration <6 months

• Adverse-risk per European Leukemia Network genetic risk stratification

• Age 18-75 years

• ECOG performance status of 0-2

Parts D and F Inclusion Criteria

• Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria)

• Disease which has relapsed, failed to respond after minimum of 6 cycles, or progressed following an HMA in the immediately preceding line of therapy.

• Eligible for continued therapy with azacitidine

• ECOG Performance Status 0-2

Parts D and E Inclusion Criteria

• Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria), previously untreated.

• Participants with higher-risk per IPSS-M MDS and MDS/AML

• ECOG Performance Status 0-2

Part G Inclusion Criteria

• Participants with diagnosis of AML (ICC 2022 criteria), previously untreated and ineligible for standard induction chemotherapy.

• Age ≥18 years.

• ECOG Performance Status of 0-2.

Exclusion Criteria (All Parts)

• Previous exposure to CD70-targeted agents

• Prior allogeneic hematopoietic stem cell transplant, for any condition

• Central nervous system leukemia

• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura

• Parts D, F and G only: Prior oral HMA or oral HMA-combinations

• Part G: conditions that preclude enteral route of administration; concomitant use of strong/moderate CYP3A inducers; history of myeloproliferative neoplasm