A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome

Inclusion criteria

[Tolerability Assessment Part】

• Patients aged 20 years or older
• Patients with a diagnosis of MDS (refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T], or chronic myelomonocytic leukemia [CMML]) according to the French-American-British (FAB) classification. Low-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 if they are unlikely to respond to any other treatment or if they are currently being treated with AZA injection.
• Patients with an ECOG PS score of 0 or 1
• Patients with adequate organ function as indicated below

• 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: The following criteria must be satisfied
• 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 informed consent form approved by the institutional review board

[Expansion Assessment Part]

• Patients aged 20 years or older
• Patients with a diagnosis of MDS (RA, RARS, RAEB, RAEB-T, or CMML) according to the FAB classification, who are categorized as Int-2 or high risk according to the IPSS
• Patients with an ECOG PS score of 0 or 1
• Patients with adequate organ function as indicated below

• Hepatic function: All of the following criteria must be satisfied
• Total bilirubin ≤ 2.0 ×ULN
• AST ≤ 2.5 × ULN
• ALT ≤ 2.5 × ULN 2. Renal function: The following criteria must be satisfied
• 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 informed consent form approved by the institutional review board

Exclusion criteria

[Tolerability Assessment Part]

• 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 disease within 3 weeks prior to the first administration of the investigational medicinal product (IMP)
• Patients who have used any other IMP or any privately imported medicine within 4 weeks prior to the first administration of IMP
• Patients with heart disease of Class 3 or 4 according to the New York Heart Association 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 other factors (including laboratory abnormalities) that, in the opinion of the investigator, are likely to affect their safety or the absorption and metabolism of AZA and 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 cancer stabilized by endocrine therapies; and malignancies that have not relapsed for at least 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 of the primary disease. However, the parameters defined in inclusion criterion 4) above are excluded.
• Patients who have undergone a highly invasive and extensive surgical procedure within 4 weeks prior to the first administration of IMP
• Patients who previously underwent hematopoietic stem cell transplantation and have evidence of graft-versus-host disease (GVHD), or who received immunotherapy within 3 weeks before the start of study treatment.
• Patients with a history of hypersensitivity to the active ingredient or any excipient of IMP
• Patients who are, in the opinion of the investigator, at high risk for being unable to comply with the trial protocol because of mental disorders or other medical conditions (alcohol/substance abuse or addiction)
• Pregnant or nursing female patients, or female patients with a positive pregnancy test at screening
• Sexually active males (except those with a history of bilateral orchiectomy) or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 3 months (males) and 6 months (females) after the last dose of IMP
• Patients who, in the opinion of the investigator, are otherwise ineligible to participate in the trial

[ Expansion Assessment Part]

• 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 disease within 3 weeks prior to the first administration of the IMP
• Patients who have received prior treatment with DNA methylation inhibitors, such as decitabine or AZA
• Patients who have used any other IMP or any privately imported medicine within 4 weeks prior to the first administration of IMP
• Patients with heart disease of Class 3 or 4 according to the New York Heart Association 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 other factors (including laboratory abnormalities) that, in the opinion of the investigator, are likely to affect their safety or the absorption and metabolism of AZA and 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 cancer stabilized by endocrine therapies; and malignancies that have not relapsed for at least 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 of the primary disease. However, the parameters defined in inclusion criterion 4) above are excluded.
• Patients who have undergone a highly invasive and extensive surgical procedure within 4 weeks prior to the first administration of IMP
• Patients who previously underwent hematopoietic stem cell transplantation and have evidence of GVHD, or who received immunotherapy within 3 weeks before the start of study treatment
• Patients with a history of hypersensitivity to the active ingredient or any excipient of IMP
• Patients who are, in the opinion of the investigator, at high risk for being unable to comply with the trial protocol because of mental disorders or other medical conditions (alcohol/substance abuse or addiction)
• Pregnant or nursing female patients, or female patients with a positive pregnancy test at screening
• Sexually active males (except those with a history of bilateral orchiectomy) or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 3 months (males) and 6 months (females) after the last dose of IMP
• Patients who, in the opinion of the investigator, are otherwise ineligible to participate in the trial