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