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

NCT04256317 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ASTX030-012024-515098-93
• Study Type: interventional
• Target: 316
• Locations: 10 countries
• Sites: 71

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myelodysplastic Syndrome/Neoplasm; Chronic Myelomonocytic Leukemia

Keywords

ASTX030; Myeloid Neoplasm; Hematologic Disease; Leukemia; Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML); Vidaza™; Azacitidine; Azacitidine and cedazuridine drug combination; Venetoclax; Venclexta™

Outcome Measures

Primary Outcomes (7)

• 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 and 2 Combination Therapy: Complete Response (CR) Rate as Assessed by the Investigator

  Up to 36 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

Secondary Outcomes (34)

• 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

  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

  Up to 36 months

• Phase 1, 2 and 3 Monotherapy: Duration of Response

  Up to 36 months

Study Arms (6)

Phase 1 Monotherapy , Stage A (Dose Escalation)

EXPERIMENTAL

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: Azacitidine; Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine

Phase 1 Monotherapy, Stage B (Dose Expansion)

EXPERIMENTAL

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: Azacitidine; Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine

Phase 2 Monotherapy, Part B, Sequence A & B

EXPERIMENTAL

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); Drug: Azacitidine

Phase 3 Monotherapy, Sequence A & B

EXPERIMENTAL

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); Drug: Azacitidine

Phase 1 Combination Therapy

EXPERIMENTAL

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); Drug: Azacitidine; Drug: Venetoclax

Phase 2 Combination Therapy

EXPERIMENTAL

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); Drug: Venetoclax

Interventions

Cedazuridine DRUG

Tablets for oral administration.

Phase 1 Monotherapy , Stage A (Dose Escalation); Phase 1 Monotherapy, Stage B (Dose Expansion)

Venetoclax DRUG

Oral tablets.

Also known as: Venclexta™

Phase 1 Combination Therapy; Phase 2 Combination Therapy

ASTX030 (cedazuridine + azacitidine) DRUG

FDC Capsules for oral administration.

Phase 1 Combination Therapy; Phase 2 Combination Therapy; Phase 2 Monotherapy, Part B, Sequence A & B; Phase 3 Monotherapy, Sequence A & B

Azacitidine DRUG

Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.

Also known as: Vidaza™ (powder only)

Phase 1 Monotherapy , Stage A (Dose Escalation); Phase 1 Monotherapy, Stage B (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 2 Monotherapy:
• \. 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:
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Participants with adequate organ function.
• For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
• Participants with no major surgery within 3 weeks before first study treatment.
• Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
• 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.
• Participants with projected life expectancy of at least 12 weeks.
• Phase 1 and Phase 2 Combination Therapy:
• Has histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2022 criteria (Phase 1) or 2016 criteria (Phase 2).
• Participants with projected life expectancy of at least 12 weeks.

You may not qualify if:

• All Monotherapy Phases:
• Has an active uncontrolled gastric or duodenal ulcer.
• Has poor medical risk because of other conditions.
• Has known human immunodeficiency virus (HIV) infection.
• Is known to be positive for Hepatitis B or C infection.
• Has a life-threatening illness.
• 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.
• Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
• Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
• 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.
• Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
• 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.
• Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
• Phase 1 and Phase 2 Combination Therapy:
• 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.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (71)

Keck School of Medicine of USC

Los Angeles, California, 90089, United States

RECRUITING

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

University of Emory - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02114, United States

RECRUITING

John Theurer Cancer Center / Hackensack University

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

New York University Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

Perlmutter Cancer Center - 34th Street

New York, New York, 10016, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Weill Cornell Medical Center

New York, New York, 10065, United States

WITHDRAWN

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Oregon Oncology Specialists

Salem, Oregon, 97301, United States

RECRUITING

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Baylor Research Institute dba Baylor Scott & White Research Institute

Dallas, Texas, 75204, United States

WITHDRAWN

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

RECRUITING

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Eastern Health - Health Sciences Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

RECRUITING

Fakultni Nemocnice Ostrava

Ostrava, Moravian-Silesian, 708 52, Czechia

RECRUITING

Fakultní Nemocnice Královské Vinohrady

Prague, Prague, 100 34, Czechia

RECRUITING

Vseobecna Fakultni Nemocnice v Praze

Prague, Prague, 128 08, Czechia

RECRUITING

Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole

Toulouse, Haute-Garonne, 31059, France

RECRUITING

Hôpital l'Archet

Nice, Provence-Alpes-Côte d'Azur Region, 06202, France

RECRUITING

Hôpital Saint-Louis

Paris, Île-de-France Region, 75010, France

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

NOT YET RECRUITING

Städtisches Klinikum Braunschweig

Braunschweig, Lower Saxony, 38114, Germany

RECRUITING

Universitätsklinikum Halle

Halle, Saxony-Anhalt, 06120, Germany

RECRUITING

Szent-Györgyi Albert Klinikai Központ, II. sz. Belgyógyászati Klinika és Kardiológiai Központ

Szeged, Csongrád megye, 6725, Hungary

NOT YET RECRUITING

Petz Aladár Győr-Moson-Sopron Vármegyei Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron, 9023, Hungary

RECRUITING

Debreceni Egyetem Klinikai Központ

Debrecen, Hajdú-Bihar, 4032, Hungary

RECRUITING

Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika

Budapest, 1088, Hungary

RECRUITING

Ospedale Santa Maria delle Croci di Ravenna

Ravenna, Emilia-Romagna, 48121, Italy

RECRUITING

Azienda Ospedaliero - Universitaria Careggi

Florence, Florence, 50134, Italy

RECRUITING

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, Turin, 10128, Italy

RECRUITING

Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, 28100, Italy

RECRUITING

Fondazione PTV - Policlinico Tor Vergata

Roma, 00133, Italy

RECRUITING

Umberto I - Policlinico di Roma

Roma, 00161, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

RECRUITING

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Lublin Voivodeship, 20-081, Poland

RECRUITING

Wojewódzkie Wielospecjalistyczne Centrum

Lodz, Lódzkie, 93-513, Poland

RECRUITING

Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością

Gdynia, Pomeranian Voivodeship, 81-519, Poland

RECRUITING

Institut Català d'Oncologia Badalona

Badalona, Barcelona, 08916, Spain

RECRUITING

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

NOT YET RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

RECRUITING

Institut Català d'Oncologia Girona (ICO Girona)

Girona, 17007, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

Clínica Universidad de Navarra - Madrid

Madrid, 28027, Spain

RECRUITING

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Quirónsalud Málaga

Málaga, 29004, Spain

RECRUITING

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

RECRUITING

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, England, M20 4GJ, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, England, SO16 6YD, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic; Hematologic Diseases; Leukemia

Interventions

Azacitidine; cedazuridine; venetoclax

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Anemia, Refractory; Anemia; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Taiho Oncology, Inc.

CONTACT

+1 844-878-2446; medicalinformation@taihooncology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 5, 2020
• Study Start: May 21, 2020
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); DE (4); ES (16); GB (3); HU (4); CA (2); CZ (3); FR (3); IT (9); PL (3)