A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome

Inclusion Criteria:

• Patients aged 20 years or older

• Patients with a diagnosis of MDS (refractory anemia [RA], refractory anemia withringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractoryanemia with excess blasts in transformation [RAEB-T], or chronic myelomonocyticleukemia [CMML]) according to the French-American-British (FAB) classificationLow-risk patients who fall under the risk category of low or intermediate-1 (Int-1)based on the International Prognostic Scoring System (IPSS) can be enrolled only ifthey are unlikely to respond to any other treatment or if they are currently beingtreated with azacytidine (AZA) injection

• Patients with an ECOG PS score of 0 or 1 or with an ECOG PS score of 2 due toprimary disease-associated conditions

• Patients with adequate organ function as indicated below

1. Hepatic function: All of the following criteria must be satisfied.

• Total bilirubin ≤ 2.0 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN

2. Renal function: Either of the following criteria must be satisfied.

• Serum creatinine ≤ 1.5 × ULN
• Creatinine clearance or glomerular filtration rate ≥ 50 mL/min

3. Respiratory function: percutaneous arterial oxygen saturation (SpO2) ≥ 90%

• Patients who are expected to survive for at least 3 months

• Patients who give written consent to participate in the trial using the informedconsent form approved by the institutional review board

Exclusion Criteria:

• Patients who are unlikely to respond to AZA

• Patients who have received chemotherapy, hormone therapy, antibody therapy,radiotherapy, or other exploratory anti-cancer treatments for the primary diseasewithin 3 weeks prior to the first administration of the investigational medicinalproduct (IMP)

• Patients who have used any other IMP or any privately imported medicine within 4weeks prior to the first administration of IMP

• Patients with heart disease of Class 3 or 4 according to the New York HeartAssociation classification

• Patients with uncontrolled systemic disease or active infection

• Patients with uncontrolled gastric or duodenal ulcer

• Patients with prior or current interstitial lung disease

• Patients with a history of surgical gastrectomy

• Patients with life-threatening conditions/symptoms, multiple organ failure, or otherfactors (including laboratory abnormalities) that, in the opinion of theinvestigator, are likely to affect their safety or the absorption and metabolism ofAZA and cedazuridine (CED), or influence the trial evaluation

• Patients with other malignancies (except appropriately treated basal cell carcinoma,squamous cell carcinoma, or cervical carcinoma in situ; prostate or breast cancerstabilized by endocrine therapies; and malignancies that have not relapsed for atleast 1 year since the last successful treatment)

• Patients who are positive for HIV antibody, HBV-DNA, or HCV antibody

• Patients with any ≥ Grade 2 AE (except alopecia) associated with prior treatment ofthe primary disease. However, the parameters defined in inclusion criterion aboveare excluded.

• Patients who have undergone a highly invasive and extensive surgical procedurewithin 4 weeks prior to the first administration of IMP

• Patients who previously underwent or plan on undergoing hematopoietic stem celltransplantation

• Patients with a history of hypersensitivity to the active ingredient or anyexcipient of IMP

• Patients who are, in the opinion of the investigator, at high risk for being unableto comply with the trial protocol because of mental disorders or other medicalconditions (alcohol/substance abuse or addiction)

• Pregnant or nursing female patients, or female patients with a positive pregnancytest at screening. Nursing patients cannot participate in the trial even if theydiscontinue breastfeeding. Female patients must undergo a pregnancy test to confirmthat they are not pregnant at screening. However, a pregnancy test is not necessaryfor female patients without childbearing potential (ie, patients with a history ofbilateral oophorectomy or hysterectomy or who have been postmenopausal for at least 12 months except for cases where menopause could be due to the effect ofantineoplastic treatment).

• Sexually active males (except those with a history of bilateral orchiectomy) orfemales of childbearing potential who do not agree to practice 2 different methodsof birth control or remain abstinent during the trial and for 3 months (males) and 6months (females) after the last dose of IMP. If birth control is employed, 2 of thefollowing precautions must be used: vasectomy, tubal ligation, intrauterine device,oral contraceptive, and condom (all methods approved or certified in Japan)

• Patients who, in the opinion of the investigator, are otherwise ineligible toparticipate in the trial