A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

Inclusion Criteria:

• Subject diagnosed with R/R AML or R/R higher risk MDS is defined as:

• R/R AML: Morphologically documented primary or secondary AML by the WHOcriteria (2016); and refractory to at least 2 cycles of inductionchemotherapy/not a candidate for re-induction or relapsed after achievingremission with a prior therapy; and received all standard therapies includingtargeted therapies (unless the therapy is contraindicated or intolerable) whichare known to provide clinical benefit in the opinion of the treatinginvestigator; and received salvage therapy or is not a candidate for salvagetherapy.

• R/R higher risk MDS: Has MDS by the WHO criteria (2016); and either relapsedafter achieving remission or refractory to standard therapies, including ≥ 4cycles of hypomethylating agents (unless the therapy is contraindicated orintolerable); and is classified as higher risk MDS with a score of > 3.5 byRevised International Prognostic Scoring System (IPSS-R) in MDS.

• Subject has an Eastern Cooperative Oncology Group performance status of ≤ 2.

• Subject must meet the following criteria as indicated on the clinical laboratorytests during screening period:

• Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upperlimit of normal (ULN).

• Serum total bilirubin ≤ 1.5 × ULN.

• Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of > 50mL/min as calculated by the Modification of Diet in Renal Disease equation.

• Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohortsonly.

• Subject has a life expectancy of ≥ 12 weeks at the time of screening.

• Subjects with AML must have peripheral blood absolute blast count of < 20,000/μL atC1D1. Note: Blast count can be controlled by hydroxyurea during screening period.

• Female subject is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP).

• WOCBP who agrees to follow the contraceptive guidance from the time of informedconsent through at least 180 days after final study treatment administration.

• Female subject must agree not to breastfeed starting at screening and throughout thestudy period and for 180 days after the final study treatment administration.

• Female subject must not donate ova starting at first dose of investigational product (IP) and throughout the study period and for 180 days after final study treatmentadministration.

• Male subject with female partner(s) of childbearing potential (includingbreastfeeding partner) must agree to use contraception throughout the treatmentperiod and for 180 day after final study treatment administration.

• Male subject must not donate sperm during the treatment period and for 180 daysafter the final study treatment administration.

• Male subject with pregnant partner(s) must agree to remain abstinent or use a condomfor the duration of the pregnancy throughout the study period and for 180 days afterfinal study treatment administration.

• Subject agrees not to participate in another interventional study while receivingstudy treatment in the present study.

Exclusion Criteria:

• Subject was diagnosed with acute promyelocytic leukemia.

• Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL).

• Subject has persistent non-hematological toxicities of ≥ grade 2 (National CancerInstitute's Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 5.0), with symptoms and objective findings from prior AML or MDS treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents,radiation or surgery).

• Subject has received any of the following therapies:

• Systemic immunomodulators or immunosuppressive drugs including steroids ≤ 28days prior to C1D1 (steroids can be used if not intended for treatment of AMLor MDS; steroids for AML/MDS related symptoms can be used at low doses [lessthan 10 mg/day dexamethasone]).

• Cytotoxic agents (except hydroxyurea given for controlling blast cells) ≤ 28days prior to C1D1.

• Investigational products for the treatment of AML or MDS within 5 half-livesprior to screening visit.

• Hematopoietic stem cell transplant (HSCT).

• Radiation therapy ≤ 28 days prior to C1D1.

• Subject has clinically active nervous system leukemia.

• Subject has active or prior documented autoimmune or inflammatory disordersrequiring systemic treatment.

• Subject has ongoing, untreated malignancy with the exception of the following:

• Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervicalintraepithelial neoplasia, regardless of the disease-free duration, areeligible for this study if definitive treatment for the condition has beencompleted.

• Subjects with organ-confined prostate cancer with no evidence of recurrent orprogressive disease are eligible if hormonal therapy has been initiated or themalignancy has been surgically removed or treated with definitive radiotherapy.

• Subject with left ventricular ejection fraction of < 45% on echocardiogram ormultigated acquisition scan (MUGA) performed within 28 days of screening.

• Subject has laboratory abnormalities, or clinical evidence of disseminatedintravascular coagulation, or ongoing history of coagulation disorder manifested bybleeding or clotting.

• Subject has an active uncontrolled infection.

• Subject is known to have human immunodeficiency virus infection.

• Subject has active hepatitis B or C or other active hepatic disorder.

• Subject has any condition which makes the subject unsuitable for studyparticipation.

• Subject has a known or suspected hypersensitivity to bovine-derived protein or hassuspected hypersensitivity to any ingredients of ASP7517.

• Subject is eligible for HSCT.