Study to Evaluate the Pharmacokinetics and Safety of Oral Decitabine and Cedazuridine in Cancer Patients With Hepatic Impairment

Inclusion Criteria:

• Able to understand and comply with the study procedures, understand the risksinvolved in the study, and provide legally effective informed consent before thefirst study-specific procedure; specifically able to comply with the PK assessmentschedule during the first treatment cycle.

• Participants must have histologically or cytologically confirmed malignancy asfollows:

1. A solid tumor that is metastatic or unresectable and for which standardlife-prolonging measures are not available.

2. AML or MDS.

3. A hematologic malignancy other than AML or MDS for which standardlife-prolonging measures are not available.

• For participants with AML/MDS only:

1. Cytologically or histologically confirmed diagnosis of AML (except M3 acutepromyelocytic leukemia) or MDS according to the 2008 World Health Organization (WHO) classification;

2. Participants with frontline MDS or treatment naïve AML not suitable forinduction therapy (e.g., >75 years, Eastern Cooperative Oncology Group [ECOG]performance status ≥2, severe pulmonary disorder, total bilirubin >1.5X ULN;

3. Platelet count ≥25,000/per microliter (μL);

4. Absolute neutrophil count (ANC) ≥100 cells/μL.

• For participants only with hematologic malignancies other than AML or MDS, or withsolid tumors:

1. Platelet count ≥100,000/μL;

2. ANC ≥1000 cells/μL.

• ECOG performance status of 0 to 2.

• Hepatic function defined per the National Cancer Institute Cancer Therapy EvaluationProgram (NCI CTEP) Organ Dysfunction Working Group (ODWG) as:

1. Normal hepatic function (Group A): total bilirubin ≤1X ULN; aspartateaminotransferase (AST): ≤1X ULN;

2. Moderate hepatic impairment (Group B): total bilirubin >1.5X to 3X ULN; AST:any value;

3. Severe hepatic impairment (Group C): total bilirubin >3 times ULN; AST: anyvalue.

• Adequate renal function defined as creatinine clearance (CLcr, according to theCockcroft-Gault equation) >50 mL/min.

• No major surgery within 30 days of first administration of oral decitabine andcedazuridine.

• Life expectancy of at least 3 months.

• Women of childbearing potential (according to recommendations of the Clinical TrialFacilitation Group) must not be pregnant or breastfeeding and must have a negativepregnancy test at Screening.

• Women of childbearing potential must agree to practice 1 highly effectivecontraceptive measure of birth control with low user dependency and must agree notto become pregnant for 6months after completing treatment

• Male participants with female partners of childbearing potential must agree to use amale condom and advise his partner to practice 1 highly effective contraceptivemeasure of birth control (user dependent or with low user dependency) and must agreenot to father a child while receiving treatment with oral decitabine andcedazuridine and for at least 3 months after completing treatment.

Exclusion Criteria:

• Treatment with azacitidine or decitabine within 4 weeks before Screening. Priorcytotoxic chemotherapy for AML except for hydroxyurea to control high white bloodcell (WBC) counts.

• Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia,sepsis, or systemic infection 30 days prior to first dose.

• Treatment with any investigational medicinal product (IMP), investigational therapy,chemotherapy, immunotherapy, or targeted therapy within 2 weeks or 5 half-lives,whichever is longer, before the first dose of study treatment, or ongoing clinicallysignificant adverse events from previous treatment.

• Concurrent MDS therapies, including lenalidomide, erythropoietin,cyclosporine/tacrolimus, granulocyte-colony-stimulating factor (G-CSF),granulocyte-macrophage colony-stimulating factor, etc. Prior treatment with theseagents is permitted, provided that completion is at least 1 week before the firstdose of study treatment. Short-term use of G-CSF for febrile neutropenia ispermitted at the discretion of the treating physician and should be guided byaccepted practice or institutional guidelines. Hematopoietic growth factors will notbe routinely used unless cleared by Taiho medical expert.

• Administration of live (attenuated) vaccines within 4 weeks before the firstadministration of oral decitabine and cedazuridine until after the follow-up visit.Other vaccines, e.g., inactivated or ribonucleic acid (RNA)-based, may beadministered but should not occur from 7 days before first administration of oraldecitabine and cedazuridine until after the follow-up visit.

• High medical risk because of other conditions such as uncontrolled systemicdiseases, active uncontrolled infections, or comorbidities that may put theparticipant at risk of not being able to complete at least 2 cycles of treatment.

• Conditions which likely promote delayed ventricular repolarization (QTprolongation):

1. Corrected QT interval (QTc) using Fridericia correction (QTcF) at Screening orDay -1 >450 ms for males and >470 ms for females.

2. History or disposition for torsades des pointes (TdP) (e.g., heart failure,hypokalemia, family history of long QT Syndrome).

3. Concomitant medication that prolong the QT/QTc interval.

• Cardiac abnormalities or unstable cardiovascular conditions:

1. Unstable ischemic heart disease or severe heart failure (New York HeartAssociation Class III or IV).

2. Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeatedmeasurements for systolic blood pressure ≥180 millimeters of mercury (mmHg)and/or diastolic blood pressure ≥110 mmHg; current or documented history ofrepeated clinically significant hypotension or severe episodes of orthostatichypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg).

• Known significant mental illness or other condition, such as active alcohol or othersubstance abuse or addiction, that in the opinion of the investigator predisposesthe participant to high risk of noncompliance with the protocol.

• In participants with AML/MDS, rapidly progressive or highly proliferative disease orother criteria that render the participant at high risk of requiring intensivecytotoxic chemotherapy within the next 3 months.

• Life-threatening illness or severe organ system dysfunction, such as uncontrolledcongestive heart failure or chronic obstructive pulmonary disease, or other reasonsincluding laboratory abnormalities, which, in the investigator's opinion, couldcompromise the participant's safety, interfere with the absorption or metabolism oforal decitabine and cedazuridine, or compromise completion of the study or integrityof the study outcomes.

• Untreated central nervous system (CNS) metastases. Participants with treated CNSmetastases are eligible provided they have been clinically stable for at least 4weeks before screening.

• Positive nasopharyngeal test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Day -1. Participants may be rescreened if they become SARS-CoV-2negative.

• Participants infected with human immunodeficiency virus (HIV).

• Positive blood screen for hepatitis C antibody (HCV+) and positive RNA polymerasechain reaction (PCR). Participant can be included if HCV+ but negative for RNA PCR.

• Positive blood screen for hepatitis B surface antigen (HBsAg+). Participants withpositive blood screen for hepatitis B surface antibody (HBsAb+) and negativehepatitis B core antibody (HBcAb-) can be included if negative for hepatitis Bsurface antigen (HBsAg-).

• Average intake of more than 24 units of alcohol per week for male participants and 17 units per week for female participant (1 unit of alcohol equals 10 mL of purealcohol, i.e., approximately 250 mL of beer, 75 mL of wine, or 25 mL of spirits).

• Positive drugs of abuse or alcohol test at Screening and Day -1, except for the useof prescribed and medically indicated drugs (e.g., benzodiazepines, opiates, orcannabinoids).

• Donation or loss of more than 500 mL of blood within 60 days prior to the firststudy drug administration.

• Hypersensitivity to decitabine, cedazuridine, or any of the excipients in oraldecitabine and cedazuridine.