Inclusion criteria

• Participants with cytologically/histologically confirmed MDS according to the 2016 World Health Organization (WHO) classification with the following:
  • Measurable disease per WHO MDS with excess blasts criteria as defined either:
• Participants with cytologically/histologically confirmed MDS according to the 2016 World Health Organization (WHO) classification with the following:
  • MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.
  • Treatment failure after prior hypomethylating agent (HMA) therapy for MDS, defined as one of the following:
• Must be off HMA therapy ≥ 2 weeks and must be off any other treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Part B Inclusion Criteria
• Participants with cytologically/histologically confirmed MDS according to the WHO classification with the following:
  • Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either:
• Participants with cytologically/histologically confirmed MDS according to the WHO classification with the following:
  • MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.
  • Treatment failure after prior HMA therapy for MDS defined as one of the following:
• Must be off HMA therapy ≥ 2 weeks and must be off any other systemic treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated.
• ECOG Performance Status of 0-2 Part C Inclusion Criteria
• Participants with relapsed or refractory AML according to International Consensus Classification (ICC) 2022 (except for acute promyelocytic leukemia \[APL\]):
  • Who have received either 2 or 3 previous regimens to treat active disease. Post-remission treatments, intrathecal chemotherapy, and radiotherapy are not considered previous regimens.
  • Who have received 1 previous regimen to treat active disease and have at least one of the following:
• Age 18-75 years
• ECOG performance status of 0-2 Parts D and F Inclusion Criteria
• Participants with diagnosis of MDS or MDS/AML according to 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
• Must be off any other systemic treatment for AML/MDS. Must be off HMA therapy ≥ (greater than or equal to) 2 weeks and any other systemic treatments for MDS for ≥ (greater than or equal to) 4 weeks prior to first dose of SEA-CD70
• ECOG Performance Status 0-2 Parts D and E Inclusion Criteria
• Participants with diagnosis of MDS or MDS/AML according to ICC 2022 criteria, previously untreated.
  • Participants with MDS/AML should not have AML-defining cytogenetic
• Participants with higher-risk (Moderate High, High, or Very High) per Molecular International Prognostic Scoring System (IPSS-M) MDS and MDS/AML
• ECOG Performance Status 0-2 Exclusion Criteria (All Parts)
• History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
• Previous exposure to CD70-targeted agents
• Prior allogeneic hematopoietic stem cell transplant, for any condition
• Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal fluid
• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
• Parts D and F only: Prior oral HMA or oral HMA-combinations