A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study) (AZTOUND)

A Multi-phase, Pharmacokinetics, Safety, and Efficacy Study of ASTX030 (Azacitidine and Cedazuridine) as Monotherapy in Subjects With Myeloid Neoplasm or in Combination With Venetoclax in Subjects With AML (AZTOUND Study)

Study ASTX030-01 is a multi-phase study comprising of Phases 1-3 Monotherapy arms, and Phase 1 and Phase 2 Combination Therapy arms. Phase 1 Monotherapy 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 Monotherapy is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 Monotherapy is a randomized open-label crossover study comparing the final fixed dose of oral ASTX030 to SC azacitidine. Phase 1 Combination Therapy is an open-label, multicenter, randomized, exploratory study comparing ASTX030 and SC azacitidine in combination with venetoclax in participants with treatment-naïve AML. Phase 2 Combination Therapy is an open-label, single arm, study evaluating the efficacy, safety, pharmacokinetics (PK), and drug interactions of ASTX030 in combination with venetoclax in participants with treatment-naïve AML.

The duration of this multi-phase study is approximately 8 years.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome/Neoplasm
• Intervention / Treatment: Drug: ASTX030 (cedazuridine + azacitidine); Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine; Drug: Azacitidine; Drug: Azacitidine; Drug: Venetoclax

Detailed Description

The Phase 1 and Phase 2 Monotherapy arms have completed enrollment. The Phase 3 Monotherapy, Phase 1 Combination Therapy, and Phase 2 Combination Therapy arms are open for enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 316
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Taiho Oncology, Inc.; Phone Number: +1 844-878-2446; Email: medicalinformation@taihooncology.com

Study Locations

• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Recruiting
      • Eastern Health - Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • Recruiting
      • Princess Margaret Cancer Centre
• Czechia
  • Moravian-Silesian
    • Ostrava, Moravian-Silesian, Czechia, 708 52
      • Recruiting
      • Fakultni Nemocnice Ostrava
  • Prague
    • Prague, Prague, Czechia, 100 34
      • Recruiting
      • Fakultni nemocnice Kralovske Vinohrady
    • Prague, Prague, Czechia, 128 08
      • Recruiting
      • Vseobecna fakultni nemocnice v Praze
• France
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Recruiting
      • Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole
  • Provence-Alpes-Côte d'Azur Region
    • Nice, Provence-Alpes-Côte d'Azur Region, France, 06202
      • Recruiting
      • Hôpital l'Archet
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75010
      • Recruiting
      • Hopital Saint-Louis
• Germany
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Recruiting
      • Universitatsklinikum Freiburg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Not yet recruiting
      • UniversitatsKlinikum Heidelberg
  • Lower Saxony
    • Braunschweig, Lower Saxony, Germany, 38114
      • Recruiting
      • Städtisches Klinikum Braunschweig
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Recruiting
      • Universitatsklinikum Halle
• Hungary
  • Budapest, Hungary, 1088
    • Recruiting
    • Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
  • Csongrád megye
    • Szeged, Csongrád megye, Hungary, 6725
      • Not yet recruiting
      • Szent-Györgyi Albert Klinikai Központ, II. sz. Belgyógyászati Klinika és Kardiológiai Központ
  • Győr-Moson-Sopron
    • Győr, Győr-Moson-Sopron, Hungary, 9023
      • Recruiting
      • Petz Aladár Győr-Moson-Sopron Vármegyei Egyetemi Oktató Kórház
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Recruiting
      • Debreceni Egyetem Klinikai Kozpont
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Novara, Italy, 28100
    • Recruiting
    • Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
  • Roma, Italy, 00133
    • Recruiting
    • Fondazione PTV - Policlinico Tor Vergata
  • Roma, Italy, 00161
    • Recruiting
    • Umberto I - Policlinico di Roma
  • Torino, Italy, 10126
    • Recruiting
    • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48121
      • Recruiting
      • Ospedale Santa Maria delle Croci di Ravenna
  • Florence
    • Florence, Florence, Italy, 50134
      • Recruiting
      • Azienda Ospedaliero - Universitaria Careggi
  • Turin
    • Torino, Turin, Italy, 10128
      • Recruiting
      • Azienda Ospedaliera Ordine Mauriziano di Torino
• Poland
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-081
      • Recruiting
      • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Lódzkie
    • Lodz, Lódzkie, Poland, 93-513
      • Recruiting
      • Wojewódzkie Wielospecjalistyczne Centrum
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-519
      • Recruiting
      • Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
  • Cáceres, Spain, 10003
    • Recruiting
    • Hospital San Pedro De Alcantara
  • Girona, Spain, 17007
    • Recruiting
    • Institut Català d'Oncologia Girona (ICO Girona)
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28027
    • Recruiting
    • Clínica Universidad de Navarra - Madrid
  • Madrid, Spain, 28033
    • Recruiting
    • MD Anderson Cancer Center Madrid
  • Málaga, Spain, 29004
    • Recruiting
    • Hospital Quironsalud Malaga
  • Salamanca, Spain, 37007
    • Recruiting
    • Complejo Asistencial Universitario de Salamanca - Hospital Clínico
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Institut Català d'Oncologia Badalona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra - Pamplona
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Not yet recruiting
      • Hospital Universitario Central de Asturias
• United Kingdom
  • England
    • London, England, United Kingdom, SE5 9RS
      • Recruiting
      • King's College Hospital NHS Foundation Trust
    • Manchester, England, United Kingdom, M20 4GJ
      • Recruiting
      • The Christie Nhs Foundation Trust
    • Southampton, England, United Kingdom, SO16 6YD
      • Not yet recruiting
      • University Hospital Southampton NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90089
      • Recruiting
      • Keck School of Medicine of USC
    • Orange, California, United States, 92868
      • Recruiting
      • UC Irvine Health - Chao Family Comprehensive Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami - Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • University of Emory - Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Dana-Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center / Hackensack University
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
    • Mineola, New York, United States, 11501
      • Recruiting
      • New York University Langone Hospital - Long Island
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • Recruiting
      • Perlmutter Cancer Center - 34th Street
    • New York, New York, United States, 10065
      • Withdrawn
      • Weill Cornell Medical Center
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
    • Salem, Oregon, United States, 97301
      • Recruiting
      • Oregon Oncology Specialists
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Hollings Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75204
      • Withdrawn
      • Baylor Research Institute dba Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Phase 2 Monotherapy:

  1. Has Confirmed MDS, CMML, or other MDS/MPN 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 Monotherapy:

  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. Is able to swallow the number of tablets/capsules required for the treatment assignment within a 10-minute period and tolerate 4 hours of fasting.
  8. Participants with projected life expectancy of at least 12 weeks.

• Phase 1 and Phase 2 Combination Therapy:

  1. Has histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2022 criteria (Phase 1) or 2016 criteria (Phase 2).
  2. Participants with projected life expectancy of at least 12 weeks.

  3. Must be considered ineligible for intensive induction chemotherapy defined by the following:

     a. Aged 75 years or older, or b. Aged 18 to 74 years with at least one of the following comorbidities: i. Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).

     ii. Severe pulmonary disorder (e.g., diffusing capacity of the lung for carbon monoxide (DLCO) ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%). iii. Creatinine clearance ≥30 mL/min to <45 mL/min. iv. Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal (ULN).

     v. ECOG Performance Status of 2 or 3.

  4. Has an ECOG Performance Status of 0-2 for participants ≥75 years of age or 0-3 for participants 18 to 74 years of age.

Exclusion Criteria:

• All Monotherapy Phases:

  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.
  11. Cannot discontinue treatment with any drugs that delay gastric emptying such as glucagon-like peptide-1 (GLP-1) and/or gastric inhibitory polypeptide (GIP) agonists in Cycles 1 and 2 of the study.
  12. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.

• Phase 1 and Phase 2 Combination Therapy:

  1. Has a history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
  2. Has the following karyotype abnormalities: t(15;17) or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy [t(8;21) and inv(16) are excluded in Phase 2 only].
  3. Has known active central nervous system involvement from AML.
  4. Has known human immunodeficiency virus (HIV) infection.
  5. Is known to be positive for Hepatitis B or C infection.
  6. Has severe hepatic impairment
  7. Has severe renal impairment
  8. Has a malabsorption syndrome or other condition that precludes enteral route of administration.
  9. Has a cardiovascular disability status of New York Heart Association Class >2.
  10. Has significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease; or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in this study.
  11. Has clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
  12. 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.
  13. Has a WBC count >25,000/ microliters (μL) (hydroxyurea treatment is permitted to meet this criterion).

  14. Has received treatment with any of the following:

      1. A hypomethylating agent (azacitidine or decitabine) or venetoclax, including prior treatment for MDS.
      2. Chimeric Antigen Receptor (CAR)-T cell therapy.
      3. Investigational therapies for MDS or AML.

  15. Cannot discontinue treatment with any of the following:

      1. Prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 halflives, whichever is greater, prior to Cycle 1 Day 1 (C1D1).
      2. Drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1.
  16. Cannot avoid concomitant drugs known as moderate or strong CYP3A inducers.
  17. Cannot discontinue treatment with any drugs that delay gastric emptying such as GLP-1 and/or GIP agonists in Cycles 1 and 2 of the study.
  18. Is participating in another research study requiring interventions such as drug therapy or study procedures.
  19. Has a known or suspected hypersensitivity to cedazuridine, azacitidine, venetoclax, or any of their excipients.
  20. Has known significant mental illness or other conditions such as alcohol or other substance abuse or addictions
  21. Consumes grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Monotherapy , Stage A (Dose Escalation); 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.	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Cedazuridine; Tablets for oral administration.; Drug: Azacitidine; Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Azacitidine; Powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only)
Experimental: Phase 1 Monotherapy, Stage B (Dose Expansion); 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.	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Cedazuridine; Tablets for oral administration.; Drug: Azacitidine; Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Azacitidine; Powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only)
Experimental: Phase 2 Monotherapy, Part B, Sequence A & B; 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).	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Azacitidine; Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Azacitidine; Powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only)
Experimental: Phase 3 Monotherapy, Sequence A & B; 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).	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Azacitidine; Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Azacitidine; Powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only)
Experimental: Phase 1 Combination Therapy; Treatment Arm 1: Participants will receive oral dose of ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). Treatment Arm 2: Participants will receive SC azacitidine along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive SC azacitidine along with oral dose of venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). At the beginning of Cycle 5, Arm 2 patients may be permitted to cross over to Arm 1.	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Azacitidine; Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Azacitidine; Powder for reconstitution to aqueous suspension for SC administration.; Other Names: Vidaza™ (powder only); Drug: Venetoclax; Oral tablets.; Other Names: Venclexta™
Experimental: Phase 2 Combination Therapy; Participants will receive ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2).	Drug: ASTX030 (cedazuridine + azacitidine); FDC Capsules for oral administration.; Drug: ASTX030 (cedazuridine + azacitidine); Tablets/Capsules for oral administration.; Drug: Venetoclax; Oral tablets.; Other Names: Venclexta™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1, 2 and 3 Monotherapy: Total Cycle Area Under the Curve (AUC) From 0 to 24 Hours (AUC0-24) Exposures	Ratio of azacitidine total cycle AUC0-24 exposures after oral ASTX030 over SC azacitidine.	Predose and at multiple timepoints post-dose up to 24 hours
Phase 1 Combination Therapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Up to 24 months
Phase 1 Combination Therapy: AUC0-24 of Venetoclax With ASTX030		Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] of Cycle 1
Phase 1 Combination Therapy: AUC0-24 of Venetoclax Without ASTX030		Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 14 (without ASTX030) of Cycle 1
Phase 1 Combination Therapy: Maximum Plasma Concentration (Cmax) of Venetoclax With ASTX030		Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] of Cycle 1
Phase 1 Combination Therapy: Cmax of Venetoclax Without ASTX030		Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 14 (without ASTX030) of Cycle 1
Phase 1 and 2 Combination Therapy: Complete Response (CR) Rate as Assessed by the Investigator		Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1, 2 and 3 Monotherapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Up to 36 months
Phase 1, 2 and 3 Monotherapy: Change in Deoxyribonucleic Acid (DNA) Methylation	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).	Baseline in Phase 1 to the end of Cycle 2 in Phase 3 (28 days per cycle)
Phase 1, 2 and 3 Monotherapy: Best CR Rate in Participants with MDS, CMML, or MDS/Myeloproliferative Neoplasms (MPN)		Up to 36 months
Phase 1, 2 and 3 Monotherapy: AML-free Survival for Participants with MDS, CMML, or MDS/MPN	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	Up to 36 months
Phase 1, 2 and 3 Monotherapy: Duration of Response	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	Up to 36 months
Phase 1, 2 and 3 Monotherapy: Overall Survival	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	Up to 36 months
Phase 1, 2 and 3 Monotherapy: Time to Response	Number of days from the start of treatment until the participant's first day of best response	Up to 36 months
Phase 1, 2 and 3 Monotherapy: Red Blood Cell (RBC) Transfusion Independence (TI)	Number of participants with RBC TI, defined as no RBC transfusion for 56 consecutive days while maintaining hemoglobin ≥8 g/dL	Up to 36 months
Phase 1, 2 and 3 Monotherapy: Platelet Transfusion Independence (TI)	Number of participants with platelet TI, defined as no platelet transfusion for 56 consecutive days while maintaining platelets ≥20×10^9/L	Up to 36 months
Phase 1, 2 and 3 Monotherapy: AUC of 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 Monotherapy: Cmax of 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 Monotherapy: Time to Reach Cmax (Tmax) of 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 1B, Food Effect Cohort: AUC of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B Monotherapy, Food Effect Cohort: Cmax of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B Monotherapy, Food Effect Cohort: Tmax of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1 Combination Therapy: AUC of SC Azacitidine and Venetoclax		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: AUC of Venetoclax, Azacitidine, and Cedazuridine		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Cmax of SC Azacitidine and Venetoclax		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Cmax of Venetoclax, Azacitidine, and Cedazuridine		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Tmax of Venetoclax, Azacitidine, and Cedazuridine		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: AUC0-24 of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose up to 24 hours on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: Cmax of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: Tmax of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: AUC0-9 of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose up to 9 hours on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: AUC0-inf of Azacitidine, Cedazuridine and Cedazuridine-epimer		Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: CR and Complete Response with Partial Hematologic Recovery (CRh) Rate		Up to 36 months
Phase 1 and 2 Combination Therapy: CR and Complete Response with Incomplete Hematologic Recovery (CRi) Rate		Up to 36 months
Phase 1 and 2 Combination Therapy: Time to CR and CRh		Up to 36 months
Phase 2 Combination Therapy: AUC0-24 of Venetoclax With and Without ASTX030		Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] and Day 14 (without ASTX030) of Cycle 1
Phase 2 Combination Therapy: Cmax of Venetoclax With and Without ASTX030		Time Frame: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] and Day 14 (without ASTX030) of Cycle 1
Phase 2 Combination Therapy: Number of Participants with TEAEs		Up to 36 months
Phase 2 Combination Therapy: Overall Survival (OS)		Up to 36 months
Phase 2 Combination Therapy: Event Free Survival (EFS)		Up to 36 months
Phase 2 Combination Therapy: Duration of CR and CRi or CRh		Up to 36 months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Leukemia; Venetoclax; Azacitidine; Myelodysplastic Syndrome (MDS); Acute Myeloid Leukemia (AML); Hematologic Disease; Myeloid Neoplasm; Chronic Myelomonocytic Leukemia (CMML); Vidaza™; ASTX030; Azacitidine and cedazuridine drug combination; Venclexta™
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Anemia; Anemia, Refractory; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Hematologic Diseases; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax; cedazuridine
• Other Study ID Numbers: ASTX030-01; 2024-515098-93 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No