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

For people ages 18 years and up

Part A Inclusion Criteria

• Participants with cytologically/histologically confirmed myelodysplastic syndrome (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% 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 (e.g., G-CSF, erythropoietin and thrombopoietin) 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 acute myeloid leukemia (AML) according to the

WHO 2016 classification (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 Net (ELN) genetic risk stratification
• Secondary AML (prior history of MDS or therapy-related)
• Age 18-75 years
• ECOG performance status of 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