ASTX727 for Leukemia

Enrolling by invitation at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiho Oncology, Inc.

Must be taking: ASTX727

Must not be taking: Investigational drugs

Disqualifiers: HIV, Hepatitis B/C, Uncontrolled infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the long-term safety of ASTX727, a combination of Decitabine and Cedazuridine, for individuals with certain blood disorders, such as leukemia. It specifically targets those who participated in previous ASTX727 studies and are responding well to the treatment. Participants will continue taking ASTX727 to assess its ongoing safety. This trial is ideal for those who have used ASTX727 in earlier trials and are benefiting from it. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently receiving hypomethylating agent (HMA) treatment, you must complete the ongoing treatment cycle before enrolling in this study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ASTX727, a combination of decitabine and cedazuridine, is generally safe for people. In earlier studies, it demonstrated a safety profile similar to other treatments for related conditions. For example, one study found that most older patients with acute myeloid leukemia, a type of blood cancer, tolerated ASTX727 well.

Some side effects were reported, but they were not unusual compared to other treatments. Importantly, the treatment was safe enough to continue in further studies. This ongoing research helps doctors understand the treatment's long-term effects and ensures its safety for extended use.

Since this study is in a later phase, earlier tests have shown the treatment to be reasonably safe. However, always consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Unlike other treatments for leukemia, ASTX727 combines two active ingredients: cedazuridine and decitabine. This combination allows for oral administration, which is a big shift from the traditional intravenous chemotherapy treatments. Researchers are excited because this oral option could make treatment more accessible and convenient for patients, potentially improving adherence and overall outcomes. Additionally, the combination aims to enhance the effectiveness of decitabine by preventing its breakdown in the body, potentially leading to better results.

What evidence suggests that ASTX727 might be an effective treatment for leukemia?

Research has shown that ASTX727, a combination of decitabine and cedazuridine, is effective for patients with leukemia. In one study, 67% of patients responded positively to the treatment, with 40% experiencing complete remission, meaning their disease disappeared. Another study found a 76% overall response rate, with 21% of patients achieving complete remission. This treatment blocks certain enzymes that cancer cells need to grow, helping to stop the disease. These results suggest that ASTX727 could be a promising option for treating leukemia. Participants in this trial will receive ASTX727 under different conditions, such as with a high-calorie/high-fat or low-calorie/low-fat breakfast meal, to evaluate its effectiveness and safety. ^{1 2 3 6 7}

Who Is on the Research Team?

Yuri Sano

Principal Investigator

Astex Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for people who have certain types of leukemia or preleukemia and were previously benefiting from ASTX727 in an Astex-sponsored study. They must understand the study, not be pregnant or breastfeeding, use effective birth control, have a performance status of 0 to 2 (which measures how the disease affects daily living abilities), and adequate liver and kidney function.

Inclusion Criteria

I am not pregnant or breastfeeding, and I agree to use 2 forms of birth control during and after treatment.

My liver and kidney functions are within the required range.

I have been diagnosed with a specific type of blood cancer and cannot undergo intensive chemotherapy.

Exclusion Criteria

I have other serious health issues that are not under control.

I do not have any severe illnesses or conditions that could risk my safety in the study.

I haven't taken any experimental drugs recently or have ongoing side effects from them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive ASTX727 once daily on Days 1 through 5 in 28-day cycles, continuing the regimen from their parent study.

Up to 2 years

1 visit per 28-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Open-label extension

Participants continue long-term treatment with ASTX727 to obtain long-term safety information.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ASTX727

Trial Overview The trial continues treatment with ASTX727 for those who benefited from it before. It also studies how food affects the drug's absorption and safety by comparing its effects when taken with different meals versus no meal at all.

How Is the Trial Designed?

Group I: Substudy Arm B: ASTX727 With Low-Calorie/Low-Fat Breakfast Meal on Day 4 Experimental Treatment 1 Intervention

Participants received ASTX727 once daily on Days 1 through 5 in a 28-day cycle (Cycle 1). Participants fasted for at least 2 hours before and 2 hours after dosing on Days 1, 3, 5 and for at least 10 hours before and 4 hours after dosing on Day 2. Participants received low-calorie/low-fat breakfast meal after an overnight fast of at least 10 hours before dosing on Day 4 and will continue to fast for at least 4 hours post-dose. Participants continued treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727 unless there was occurrence of disease progression requiring alternative therapy, unacceptable toxicity, noncompliance, a decision to discontinue treatment, or if the participant withdraws from the study.

Group II: Substudy Arm A: ASTX727 With High-Calorie/High-Fat Breakfast Meal on Day 4 Experimental Treatment 1 Intervention

Participants received ASTX727 once daily on Days 1 through 5 in a 28-day cycle (Cycle 1). Participants fasted for at least 2 hours before and 2 hours after dosing on Days 1, 3, 5 and for at least 10 hours before and 4 hours after dosing on Day 2. Participants received a high-calorie/high-fat breakfast meal after an overnight fast of at least 10 hours before dosing on Day 4 and continued to fast for at least 4 hours post-dose. Participants continued treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727 unless there was occurrence of disease progression requiring alternative therapy, unacceptable toxicity, noncompliance, a decision to discontinue treatment, or if the participant withdraws from the study.

Group III: Main Extension Study: ASTX727 Experimental Treatment 1 Intervention

The recommended starting dose is the fixed-dose combination (FDC) standard dose (SD) tablet, containing 100 mg cedazuridine and 35 mg decitabine, once daily, Days 1 through 5 in 28-day cycles. Participants should receive ASTX727 at the same dose they received in the last cycle of their parent study; if an adjustment from that dose is required, a different total cycle dose may be employed, as guided by the dose adjustment guidelines in the parent study protocol.

ASTX727 is already approved in United States, European Union for the following indications:

Approved in United States as Inqovi for:

• Myelodysplastic Syndromes (MDS)

Approved in European Union as Inqovi for:

• Myelodysplastic Syndromes (MDS)

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Astex Pharmaceuticals, Inc.

Lead Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

Oral azacitidine (CC-486) has been shown to improve overall survival as maintenance therapy for older patients with acute myeloid leukemia who are in complete remission, highlighting its efficacy in this specific patient population.

The combination of decitabine and cedazuridine (ASTX727) is approved for treating adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, particularly those with intermediate-1 or higher risk, indicating its targeted therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. Kipp, D., H Wei, A.[2022]

Decitabine is an effective hypomethylating agent for treating acute myeloid leukemia (AML), significantly improving overall survival and response rates compared to standard care, based on results from the phase 3 DACO-016 trial with adult patients who are not eligible for standard chemotherapy.

The treatment is generally well tolerated and remains effective even in patients with adverse-risk karyotypes or TP53 mutations, making it a valuable option for those unfit for more intensive therapies, with potential for future combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. Santini, V., Lübbert, M., Wierzbowska, A., et al.[2022]

In a study of 8 geriatric patients with acute myeloid leukemia, treatment with decitabine, with or without low-dose cytarabine, resulted in a 50% overall response rate, with 25% achieving complete remission and 25% achieving partial remission.

The treatment showed a median overall survival time of 9.5 months, with some patients surviving over a year, although it was associated with significant side effects, including severe myelosuppression in 87.5% of patients and pneumonia in 50%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia]. Zhou, HW., Zhou, MH., Wang, ZH., et al.[2019]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

In a phase 1 study involving 44 patients with myelodysplastic syndromes or chronic myelomonocytic leukaemia, the combination of oral decitabine and the CDA inhibitor cedazuridine successfully increased the bioavailability of decitabine, achieving pharmacokinetics similar to intravenous administration without increasing toxicity.

The study demonstrated that oral decitabine combined with cedazuridine produced effective dose-dependent demethylation and clinical responses comparable to intravenous decitabine, suggesting it could be a viable alternative treatment for myeloid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Savona, MR., Odenike, O., Amrein, PC., et al.[2019]

Decitabine has been approved for treating older patients (65 years and older) with newly diagnosed acute myeloid leukemia (AML) who cannot undergo standard chemotherapy, showing a median overall survival of 7.7 months compared to 5.0 months for those receiving low-dose cytarabine or supportive care.

The treatment demonstrated improved response rates and progression-free survival, with a manageable safety profile, making it a valuable option for older patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Decitabine (Dacogen) for the Treatment of Adult Patients With Acute Myeloid Leukemia: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. Nieto, M., Demolis, P., Béhanzin, E., et al.[2018]

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

The D-CAG regimen, which combines decitabine with a modified chemotherapy approach, achieved a complete remission (CR) rate of 69.4% in 59 elderly patients (≥70 years) with newly diagnosed acute myeloid leukemia (AML), indicating its efficacy in this age group.

The treatment was found to be safe, with major adverse reactions including grade 3-4 myelosuppression and infections, but it significantly improved overall survival (OS) and event-free survival (EFS) for patients who achieved CR, with median OS of 19.8 months compared to 6.4 months for those who did not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. Cao, L., Jiang, ZQ., Liu, WJ., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8701430/

Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the ... Two patients (12.5%) had Complete Responses (CR), 8 (50%) had marrow CR ([mCR], including 3 (19%) with hematologic improvement (HI); Overall ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6551

Phase II trial of 10-day ASTX727 (decitabine/cedazuridine ... Conclusions: The 10-day ASTX727-VEN combination showed safety profile comparable to other HMA-VEN regimens in salvage setting. TP53 wild type, ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2896/533121/Fully-Oral-Combination-of-Decitabine-Cedazuridine

Fully Oral Combination of Decitabine/Cedazuridine (ASTX727 ... The median follow-up time was 20 months. The ORR was 40/60 (67%), including 24 (40%) complete remission (CR), 13 (22%) CR with incomplete count ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04657081

Study Details | NCT04657081 | Pharmacokinetics, Safety, ... The primary purpose of the study is to rule out drug-drug interactions between ASTX727 and venetoclax combination therapy by evaluating area under the curve ( ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40524338/

Efficacy and safety of oral decitabine/cedazuridine in the ... The overall response rate was 76%, with 21% (n = 7) of patients achieving a complete response. Nearly half of the 11 patients who were red blood ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/833/499481/A-Phase-2-Study-of-the-Fully-Oral-Combination-of

A Phase 2 Study of the Fully Oral Combination of ASTX727 ... 17/42 (40%) pts had antecedent MDS (including 8 [19%] with treated secondary AML) and 6/42 (14%) had therapy-related AML (t-AML). By ELN 2022, 6 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38452788/

Oral decitabine and cedazuridine plus venetoclax for older or ... ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia.