A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects with Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003281-40-DE

Enrollment

168

Registered

2021-04-30

Start date

2021-10-19

Completion date

Unknown

Last updated

2024-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS) MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851 MedDRA version: 27.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Product Name: ASTX727 LD Pharmaceutical Form: Tablet INN or Proposed INN: CEDAZURIDINE CAS Number: 1141397-80-9 Current Sponsor code: E7727 Other descriptive name: E7727

Cedazuridine [INN]

(4R)-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100- INN or Pro

4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin- 2(1H)-one Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5- Product Name: ASTX727 SD

E7727

4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin- 2(1H)-one Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 35- Product Name: Decitabine

4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin- 2(1H)-one Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5- Product Name: ASTX727 LD

Cedazuridine [I

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion Criteria Subjects must fulfill all of the following inclusion criteria. 1) Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure. 2) Men or women =18 years with IPSS low risk or Int-1 MDS (all subjects). Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization: a) RBC transfusion dependence, defined as 2 or more units of RBC transfusions.* b) Hb of =9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received. c) ANC of =65 years) yes F.1.3.1 Number of subjects for this age range 144

Exclusion criteria

Exclusion criteria: Subjects meeting any of the following exclusion criteria will be excluded from the study: 1. Treatment with any investigational drug or therapy within 2 weeks before study treatment, or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant AEs from previous treatment. 2. Prior treatment with azacitidine, decitabine or gaudecitabine. 3. Treatments for MDS, including erythropoietins, colony-stimulating factors (CSFs), thrombopoietins, chemotherapy, and immunosuppression including calcineurin inhibitors, glucocorticoids, etc., must be concluded 1 month prior to study treatment. 4. Diagnosis of chronic myelomonocytic leukemia (CMML). 5. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections. 6. Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the subject to high risk of noncompliance with the protocol. 7. Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ASTX727 LD, or compromise the integrity of the study outcomes. 8. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 1 year. 9. Known active infection with human immunodeficiency virus or hepatitis viruses.

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase 1: - to assess the safety profile of doses and schedules of ASTX727. - to select the ASTX727 dose(s) and schedule(s) to study in Phase 2. Phase 2: - to assess the clinical efficacy of ASTX727 dose(s) and schedule(s) studied.;Secondary Objective: Phase 1: - to assess the pharmacodynamic (PD) activity of doses and schedules of ASTX727. - to characterize the pharmacokinetics (PK) of decitabine, cedazuridine, and its metabolite cedazuridine-epimer. - to assess hematologic response. Phase 2: - to assess the safety of the ASTX727 dose(s) and schedule(s) studied. - to assess PD activity and PK of decitabine at the ASTX727 dose(s) and schedule(s) studied. ;Primary end point(s): Primary Endpoints Phase 1 ·Safety as determined by incidence of drug-related Grade =3 AEs or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule. Phase 2 ·Hematologic response as defined in the Efficacy Analysis section. ;Timepoint(s) of evaluation of this end point: The DSRC will comprise the principal investigators (or nominated deputies), medical monitor, study director, PD director, PK director, and other team members as appropriate. Safety, PD, and other clinical data from this study will be assessed for each dose cohort by the DSRC after at least Cycle 1 of Phase 1 Stage A and after at least Cycle 1 of Phase 1 Stage B. The DSRC will recommend the dose(s)/schedule(s) to be taken forward to Phase 2. In Phase 2, the DSRC will review emerging safety data in the first 6 subjects enrolled into the ASTX727 SD Daily×3 dose regimen and expand this safety evaluation to 12 subjects if necessary. The DSRC will also review the data when at least 20 subjects in each regimen have been followed up for at least 1 cycle of safety data, or earlier if warranted.	—

Measure

Time frame

Main Objective: Phase 1: - to assess the safety profile of doses and schedules of ASTX727. - to select the ASTX727 dose(s) and schedule(s) to study in Phase 2. Phase 2: - to assess the clinical efficacy of ASTX727 dose(s) and schedule(s) studied.;Secondary Objective: Phase 1: - to assess the pharmacodynamic (PD) activity of doses and schedules of ASTX727. - to characterize the pharmacokinetics (PK) of decitabine, cedazuridine, and its metabolite cedazuridine-epimer. - to assess hematologic response. Phase 2: - to assess the safety of the ASTX727 dose(s) and schedule(s) studied. - to assess PD activity and PK of decitabine at the ASTX727 dose(s) and schedule(s) studied. ;Primary end point(s): Primary Endpoints Phase 1 ·Safety as determined by incidence of drug-related Grade =3 AEs or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule. Phase 2 ·Hematologic response as defined in the Efficacy Analysis section. ;Timepoint(s) of evaluation of this end point: The DSRC will comprise the principal investigators (or nominated deputies), medical monitor, study director, PD director, PK director, and other team members as appropriate. Safety, PD, and other clinical data from this study will be assessed for each dose cohort by the DSRC after at least Cycle 1 of Phase 1 Stage A and after at least Cycle 1 of Phase 1 Stage B. The DSRC will recommend the dose(s)/schedule(s) to be taken forward to Phase 2. In Phase 2, the DSRC will review emerging safety data in the first 6 subjects enrolled into the ASTX727 SD Daily×3 dose regimen and expand this safety evaluation to 12 subjects if necessary. The DSRC will also review the data when at least 20 subjects in each regimen have been followed up for at least 1 cycle of safety data, or earlier if warranted.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary Endpoints - RBC transfusion independence, as defined in Efficacy Analysis section; - Platelet transfusion independence, as defined in Efficacy Analysis section; - Overall response rate (ORR): complete response (CR), marrow complete response (mCR), and hematologic improvement (HI) based on International Working Group IIWG) 2006 MDS response criteria, as defined in Section 11.6; - %LINE-1 methylation change from baseline; - PK parameters, including area under the curve (AUC), maximum concentration (Cmax), Tmax, and t1/2 of decitabine, cedazuridine, and cedazuridine-epimer in the first cycle of treatment; - Safety as determined by incidence of AEs, AEs of Grade =3, and serious adverse events (SAEs) (Primary endpoint for Phase 1); - Hematologic response (Secondary endpoint for Phase 1 only); - HbF induction compared with baseline to >1% from =1%, or increase of 50% in subjects with =1% at baseline in at least 2 successive measurements; - Time to bone marrow blasts >5%, defined as the number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by =50%; - Leukemia-free survival, defined as the number of days from the date of randomization to the date when bone marrow or peripheral blood blasts reach =20%, or death from any cause; - Overall survival (OS), defined as the number of days from the date of randomization to the date of death from any cause.;Timepoint(s) of evaluation of this end point: During the course of the study, emerging safety data will be considered by the DSRC in evaluating the potential risks and benefits of ASTX727 LD. In Phase 1, cohorts in which =33% of subjects are observed to have DLTs will stop further enrollment and not be taken forward to Phase 2. During the conduct of the study, cohorts may be discontinued from treatment with study drug for safety (including, but not limited to DLTs) after review by the DSRC.	—

Measure

Time frame

Secondary end point(s): Secondary Endpoints - RBC transfusion independence, as defined in Efficacy Analysis section; - Platelet transfusion independence, as defined in Efficacy Analysis section; - Overall response rate (ORR): complete response (CR), marrow complete response (mCR), and hematologic improvement (HI) based on International Working Group IIWG) 2006 MDS response criteria, as defined in Section 11.6; - %LINE-1 methylation change from baseline; - PK parameters, including area under the curve (AUC), maximum concentration (Cmax), Tmax, and t1/2 of decitabine, cedazuridine, and cedazuridine-epimer in the first cycle of treatment; - Safety as determined by incidence of AEs, AEs of Grade =3, and serious adverse events (SAEs) (Primary endpoint for Phase 1); - Hematologic response (Secondary endpoint for Phase 1 only); - HbF induction compared with baseline to >1% from =1%, or increase of 50% in subjects with =1% at baseline in at least 2 successive measurements; - Time to bone marrow blasts >5%, defined as the number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by =50%; - Leukemia-free survival, defined as the number of days from the date of randomization to the date when bone marrow or peripheral blood blasts reach =20%, or death from any cause; - Overall survival (OS), defined as the number of days from the date of randomization to the date of death from any cause.;Timepoint(s) of evaluation of this end point: During the course of the study, emerging safety data will be considered by the DSRC in evaluating the potential risks and benefits of ASTX727 LD. In Phase 1, cohorts in which =33% of subjects are observed to have DLTs will stop further enrollment and not be taken forward to Phase 2. During the conduct of the study, cohorts may be discontinued from treatment with study drug for safety (including, but not limited to DLTs) after review by the DSRC.

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Countries

Belgium, Canada, Germany, Italy, Spain, United Kingdom

Contacts

Public ContactRegulatory Affairs

Taiho Oncology, Inc.

ellee@taihooncology.com+14089219779

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026