A Study of ASTX030 (Cedazuridine in Combination with Azacitidine) in MDS, CMML, or AML

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Taiho Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

22 Jul 2025 → ongoing

Decision date (initial)

2025-05-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Taiho Oncology, Inc.

External identifiers

EU CT number

2024-515098-93-00

ClinicalTrials.gov

NCT04256317

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Dose response, Therapy, Pharmacokinetic, Efficacy

• Establish azacitidine AUC equivalence (90% CI 0.8, 1.25) between the final selected dose of ASTX030 from Phase 2 using FDC and SC azacitidine at 75 mg/m2/day across BSA ranges

Secondary objectives 4

1. • Assess safety and tolerability of ASTX030
2. • Evaluate changes in DNA methylation of ASTX030 compared to SC azacitidine
3. • Assess clinical activity of ASTX030
4. • Evaluate other PK parameters of azacitidine, cedazuridine, and cedazuridine-epimer

Conditions and MedDRA coding

Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Must be ≥18 years
2. 10. Follow contraceptive barrier requirements per protocol
3. 11. Capable of giving legally effective informed consent. and willing to participate in the study.
4. 2. Confirmed MDS or CMML and a candidate to receive and benefit from single-agent azacitidine according to French-American-British myelodysplastic syndrome subtypes: or MDS with intermediate-2 or high risk MDS according to the IPSS (Greenberg P, et al. Blood. 1997;89:2079-2088)
5. 3. ECOG 0 or 1
6. 4. Adequate organ function : a. Total or direct bilirubin ≤2 × ULN; AST/ SGOT and ALT/SGPT ≤2.5 × ULN. b. Calculated CrCl >50 mL/min by Cockcroft-Gault formula or other medically acceptable formulas.
7. 5. For participants with prior allogeneic stem cell transplant, has no evidence of graft vs host disease and must be ≥3 weeks off systemic immunosuppressive therapy before study start.
8. 6. No major surgery within 3 weeks before treatment initiation.
9. 7. No cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before treatment initiation
10. 8. Able to swallow the number of capsules required within 10-mins and can tolerate 4 hours of fasting.
11. 9. Life expectancy >= 12 weeks.

Exclusion criteria 11

1. 1. Active, uncontrolled gastric or duodenal ulcer.
2. 6.History of other malignancies, except certain adequately treated and/or controlled cancers, or early-stage cases not requiring therapy.
3. 7. Extramedullary disease in MDS/MPN, including palpable hepatomegaly or splenomegaly
4. 8. Prior treatment with > 1 cycle of decitabine or azacitidine
5. 9. Treated with any investigational therapy within 2 weeks, or 5 half-lives, whichever is longer, before treatment initiation , or has ongoing clinically significant AEs from previous treatment with investigational agent
6. 10. Cannot discontinue treatment with drugs that delay gastric emptying (GLP-1 and/or GIP agonists in Cycles 1 & 2.
7. 11. Known hypersensitivity to cedazuridine or azacitidine or any excipients.
8. 2. Poor medical risk due to any uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.
9. 3. Known HIV infection.
10. 4. Known positive for Hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months of screening
11. 5. Life-threatening illness, uncontrolled medical condition or organ system dysfunction, or other reasons that, could compromise the participant's safety, interfere with the absorption or metabolism of ASTX030, or the integrity of study outcomes.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Ratio of azacitidine total cycle AUC 0-24 exposures after oral ASTX030 over SC azacitidine at 75 mg/m2/day

Secondary endpoints 3

1. 1 TEAEs including SAEs
2. 2 Percent LINE-1 demethylation change from baseline between SC azacitidine and ASTX030 in Cycles 1 and 2
3. 3 Participants with MDS or CMML: - Clinical response rate - AML-free survival - Duration of response - OS - Time to response - Transfusion independence

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Taiho Oncology Inc.

Sponsor organisation

Taiho Oncology Inc.

Address

101 Carnegie Center Suite 300

City

Princeton

Postcode

08540-6231

Country

United States

Scientific contact point

Organisation

Taiho Oncology Inc.

Contact name

Yuri Sano

Public contact point

Organisation

Taiho Oncology Inc.

Contact name

Yuri Sano

Third parties 11

Locations

7 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications