University of Kansas Medical Center

• 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.

(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