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

Phase 2

Recruiting

• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myelodysplastic Syndrome/Neoplasm; Chronic Myelomonocytic Leukemia
• Interventions: Drug: Azacitidine; Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine

• Registration Number: NCT04256317
• Lead Sponsor: Taiho Oncology, Inc.

Brief Summary

Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of this phase 1-3 study is approximately 7 years.

Detailed Description

The Phase 1 and Phase 2 arms have completed enrollment. The Phase 3 arm is open for enrollment.

Study Timeline

• Study First Submitted: 2020-01-31
• Study First Submitted QC: 2020-02-03
• Study First Posted: 2020-02-05
• Study Start: 2020-05-21
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-02
• Primary Completion: 2027-05-01
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 235

Inclusion Criteria

Phase 2:

1. Has Confirmed MDS, CMML, MDS/MPN or AML diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice.

Phase 3:

1. Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice:

   a) French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

3. Participants with adequate organ function.

4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).

5. Participants with no major surgery within 3 weeks before first study treatment.

6. Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.

7. Participants with projected life expectancy of at least 12 weeks.

Exclusion Criteria

Phase 2 and 3:

1. Has an active uncontrolled gastric or duodenal ulcer.
2. Has poor medical risk because of other conditions.
3. Has known human immunodeficiency virus (HIV) infection.
4. Is known to be positive for Hepatitis B or C infection.
5. Has a life-threatening illness.
6. Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
7. Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
8. Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
9. Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
10. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Phase 1, Stage A (Dose Escalation)	Azacitidine	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered.
Phase 1, Stage A (Dose Escalation)	ASTX030 (cedazuridine + azacitidine)	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered.
Phase 1, Stage A (Dose Escalation)	Cedazuridine	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered.
Phase 1, Stage B (Dose Expansion)	Azacitidine	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. On Day 7 of Cycle 2 drug products will administered in a fed state and all other doses will be administered in fasted state.
Phase 1, Stage B (Dose Expansion)	ASTX030 (cedazuridine + azacitidine)	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. On Day 7 of Cycle 2 drug products will administered in a fed state and all other doses will be administered in fasted state.
Phase 1, Stage B (Dose Expansion)	Cedazuridine	In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. On Day 7 of Cycle 2 drug products will administered in a fed state and all other doses will be administered in fasted state.
Phase 2, Part B, Sequence A & B	ASTX030 (cedazuridine + azacitidine)	In Sequence A: Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
Phase 2, Part B, Sequence A & B	Azacitidine	In Sequence A: Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
Phase 3, Sequence A & B	ASTX030 (cedazuridine + azacitidine)	In Sequence A: Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
Phase 3, Sequence A & B	Azacitidine	In Sequence A: Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).

Primary Outcome Measures

Name	Time	Method
Phase 1, 2 and 3: Total Cycle Area Under the Curve (AUC) from 0 to 24 Hours (AUC0-24) Exposures	Predose and at multiple timepoints post-dose up to 24 hours	Ratio of azacitidine total cycle AUC0-24 exposures after oral ASTX030 over SC azacitidine.

Secondary Outcome Measures

Name	Time	Method
Phase 1B, Food Effect Cohort: AUC for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B, Food Effect Cohort: Cmax for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B, Food Effect Cohort: Tmax for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1, 2 and 3: Red Blood Cell (RBC) Transfusion Independence (TI)	Up to 36 months	Number of participants with RBC TI, defined as no RBC transfusion for 56 consecutive days while maintaining hemoglobin ≥8 g/dL
Phase 1, 2 and 3: Change in Deoxyribonucleic Acid (DNA) Methylation	Baseline in Phase 1 to the end of Cycle 2 in Phase 3 (28 days per cycle)	Percent long interspersed nuclear elements 1 (LINE-1) methylation change (demethylation) from baseline in Cycle 1 (Phase 1) and compared between SC azacitidine and ASTX030 in Cycles 1 and 2 (Phase 2 and 3).
Phase 1, 2 and 3: Duration of Response	Up to 36 months	Number of days from the date that criteria are met for response until the first date that recurrent or progressive disease is documented by the investigating physician
Phase 1, 2 and 3: AUC for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)
Phase 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to 36 months
Phase 1, 2 and 3: Best Clinical Response Rate for Participants with MDS, CMML, or MDS/Myeloproliferative Neoplasms (MPN)	Up to 36 months
Phase 1, 2 and 3: AML-free Survival for Participants with MDS, CMML, or MDS/MPN	Up to 36 months	Number of days from the date of randomization (date of first treatment in Phase 1) to either the date of MDS, CMML, or MDS/MPN progression to AML or the date of death from any cause
Phase 1, 2 and 3: Overall Survival	Up to 36 months	Number of days from the date the participant was randomized (date of first treatment in Phase 1) to the date of death, regardless of cause
Phase 1, 2 and 3: Time to Response	Up to 36 months	Number of days from the start of treatment until the participant's first day of best response
Phase 1, 2 and 3: Platelet Transfusion Independence (TI)	Up to 36 months	Number of participants with platelet TI, defined as no platelet transfusion for 56 consecutive days while maintaining platelets ≥20×10\^9/L
Phase 1, 2 and 3: Cmax for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)
Phase 1, 2 and 3: Time to Reach Cmax (Tmax) for Azacitidine, Cedazuridine and Cedazuridine-epimer	Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)

Trial Locations

Locations (24)

Keck School of Medicine of USC; 🇺🇸 Los Angeles, California, United States

UCI Health - Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

John Theurer Cancer Center / Hackensack University; 🇺🇸 Hackensack, New Jersey, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

New York University Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

Perlmutter Cancer Center - 34th Street; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

James P. Wilmot Cancer Center; 🇺🇸 Rochester, New York, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute; 🇺🇸 Columbus, Ohio, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Oregon Oncology Specialists; 🇺🇸 Salem, Oregon, United States

Hollings Cancer Center; 🇺🇸 Charleston, South Carolina, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Baylor Research Institute dba Baylor Scott & White Research Institute; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Froedtert & Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Eastern Health - Health Sciences Centre; 🇨🇦 St. John's, Newfoundland and Labrador, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada