Inclusion criteria

Part A 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:
    • 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood or
    • 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood
  • 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:
    • Progression (per 2006 International Working Group [IWG] criteria) at any time after initiation of HMA therapy.
    • Lack of response (failure to achieve complete remission [CR], partial response [PR], or hematologic improvement [HI] per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent HMA) or 4 cycles of decitabine (or equivalent HMA).
    • Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
    • Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).
    • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
• 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:
    • 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood, or
    • 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood
  • 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:
    • Progression (per 2006 IWG criteria) at any time after initiation of HMA therapy.
    • Lack of response (failure to achieve CR, PR, or HI per 2006 IWG criteria) after at least 6 cycles of azacitidine or 4 cycles of decitabine.
    • Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
    • Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).
    • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
• 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 > 60 and ≤75 years.
    • Primary resistant AML (defined as failure to achieve CR after 1-2 courses of induction therapy)
    • First CR duration <6 months
    • Adverse-risk per European Leukemia Network genetic risk stratification
    • Secondary AML (prior history of MDS or therapy-related)
• 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 cytogenetics.
• 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