cedazuridine/azacitidine (ASTX030) / Otsuka, Taiho - LARVOL DELTA

Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN) (ASH 2024) - P2/3 | "Background : Azacitidine (AZA) and decitabine (DEC) are parenteral DNA methyltransferase inhibitors (DNMTis) approved for the treatment of patients with MDS and acute myeloid leukemia...Median age was 72 years (range, 26–87), 35% (n=31) of patients were female, prior treatments included DNMTis (9% [n=8]), luspatercept (3% [n=3]), lenalidomide (3% [n=3]), and erythropoiesis‑stimulating agents (3% [n=2])...Based on the results of the phase 1 trial, 140/20 mg AZA/CED was selected as the RP2D. Enrollment for the phase 2 randomized, crossover (oral vs SC) trial is ongoing and combination dosing is in preparation."

Clinical • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=59 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | N=40 ➔ 59 | Trial completion date: Jan 2026 ➔ Jan 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

POOLED PHASE1/2 DATA IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) AND MDS/MYELOPROLIFERATIVE NEOPLASMS SUPPORTS A BODY SURFACE AREA (BSA)-BASED DOSING STRATEGY FOR ORAL AZACITIDINE-CEDAZURIDINE (EHA 2026) - P2/3 | "Based on Ph2 PK data, a BSA-based dosing strategy was implemented for the ongoing global Ph3 AZTOUND study. Clinical trial registration: NCT04256317"

Clinical • P1/2 data • Chronic Myelomonocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia

ASTX030-01: A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study) (clinicaltrials.gov) - P2/3 | N=316 | Recruiting | Sponsor: Taiho Oncology, Inc. | N=236 ➔ 316 | Trial completion date: May 2028 ➔ Nov 2028 | Trial primary completion date: May 2027 ➔ Nov 2027

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

A phase 2 dose confirmation trial of oral ASTX030, a combination of oral azacitidine with cedazuridine among patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia (ASH 2025) - P2/3 | "Background :Parenteral hypomethylating agents such as azacitidine (AZA) and decitabine are standard treatments formyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Oral ASTX030 showed PK, pharmacodynamic, and clinical profiles comparable to SC AZA,supporting its potential as an oral alternative. The observed variability in drug exposures, influenced bypts' BSA, highlights the value of BSA-based dosing to better align systemic exposure with that of SC AZA.The international Ph3 trial, AZTOUND, which incorporates BSA-based dosing, is currently recruitingparticipants.Clinical trial registration: NCT04256317"

Clinical • P2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia • HEY1

Authors will report results from the ASTX030-01 study of oral azacitidine and cedazuridine versus subcutaneous azacitidine in patients with MDS, CMML or AML (PRNewswire) - "As of the data cutoff, ASTX030 Phase 2 results demonstrated the following: The primary endpoint was the geometric mean ratio (GMR) of azacitidine total cycle AUC 0–24 exposures after oral ASTX030 over subcutaneous azacitidine, and the result for that endpoint was 0.913 (90% confidence interval [CI]: 0.78, 1.07); In patients with MDS (n=22), the complete response (CR) rate was 22.7% and overall response rate was 50%; Among patients who were dependent on red blood cell (RBC) transfusions at baseline (n=13), 30.8% achieved independence from RBC transfusions for 56 days or more....Adverse events (AEs) were reported in 100% of trial participants, with 83.3% of those AEs classified as grade 3 or higher."

P2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

Taiho Oncology will share findings from clinical trials in two oral presentations and evidence from real-world studies in two online abstracts. (Taiho Press Release) - "The oral presentations will highlight results from the Phase 2 part of ASTX030-01, a randomized, open-label, crossover trial comparing oral combination of azacitidine and cedazuridine to subcutaneous azacitidine and the Phase 2 portion of the Phase 1/2 trial ASTX727-03 of low-dose versus standard-dose oral decitabine and cedazuridine in patients with lower-risk myelodysplastic syndromes (MDS). The two online posters will present real-world data on U.S. adults with acute myeloid leukemia (AML), describing treatment patterns and outcomes with hypomethylating agent (HMA) plus venetoclax, and evaluating the time burden of initiating parenteral HMA-based therapy in routine practice."

Clinical data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

Development of Oral Azacitidine with Cedazuridine for Myelodysplastic Syndrome (MDS) and Myeloproliferative Neoplasms (MPN) Including CMML (Chronic Myelomonocytic Leukemia) By Targeting Pharmacokinetic AUC Equivalence Vs Subcutaneous Azacitidine (ASH 2023) - "The oral fixed-dose combination of decitabine with cedazuridine, ASTX727, was approved by regulators in the USA and Canada for patients with MDS and CMML based upon the demonstration of biologically equivalent pharmacokinetics (PK) area under the curve (AUC) vs IV decitabine. ASTX030 successfully achieved the primary endpoint of PK equivalence versus SC AZA based on total cycle AUC. The dose combinations evaluated were well tolerated, and the safety profile similar to that of SC AZA, with no unique AE's. LINE-1 demethylation and clinical response confirm the clinical activity of ASTX030."

PK/PD data • Acute Myelogenous Leukemia • Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

Real-world experience and outcomes of decitabine/cedazuridine or azacitidine for the treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia. (PubMed, Leuk Lymphoma) - No abstract available

Journal • Real-world evidence • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Trial completion date: May 2025 ➔ Jan 2026 | Trial primary completion date: Apr 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

ASTX030-01: A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML (clinicaltrials.gov) - P2/3 | N=235 | Recruiting | Sponsor: Taiho Oncology, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Apr 2026 ➔ May 2028 | Trial primary completion date: Dec 2025 ➔ May 2027

Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

Results of Phase 1 Open-Label Dose Escalation and Expansion Trial of ASTX030 (Oral Azacitidine + Cedazuridine) (PRNewswire) - P1/2/3 | N=317 | NCT04256317 | Sponsor: Taiho Oncology, Inc. | "This Phase 1 trial aimed to determine the optimal dose and formulation of ASTX030 to achieve oral azacitidine area under the curve (AUC) exposures comparable to SC azacitidine....Pharmacokinetic data showed that 20 mg of cedazuridine sufficiently prevented azacitidine from degradation during first pass in the digestive tract and liver resulting in enhanced azacitidine bioavailability, achieving AUC exposures comparable to SC azacitidine, and the dose combination of 140 mg azacitidine/20 mg cedazuridine was recommended for evaluation in Phase 2. The clinical efficacy results were consistent with parenteral azacitidine. The median overall survival was 29.5 months, with overall response rate of 56% (11% complete response, 0% partial response, 34% marrow complete response, 10% hematologic improvement), 27% stable disease, 2% progressive disease and 15% not evaluable."

P1 data • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Taiho Oncology to Present Data at the 66th American Society of Hematology Annual Meeting (PRNewswire) - "Data to be presented from an oral azacitidine plus cedazuridine (ASTX030) combination phase 1 open-label dose escalation and expansion trial; Findings to be shared from a study analyzing real–world use patterns and clinical outcomes for patients with myelodysplastic syndrome (MDS) initiating oral decitabine and cedazuridine or intravenous/subcutaneous hypomethylating agents."

P1 data • Real-world • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML (clinicaltrials.gov) - P2/3 | N=317 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2024 ➔ May 2025 | Trial primary completion date: Nov 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Development of Oral Azacitidine With Cedazuridine for Myelodysplastic Syndrome (MDS) and Myeloproliferative Neoplasms (MPN) Including Chronic Myelomonocytic Leukemia (CMML) by Targeting Pharmacokinetic AUC Equivalence vs Subcutaneous Azacitidine (SOHO 2024) - "Background: ASTX030 is a combination of AZA and cedazuridine (CED), a cytidine deaminase inhibitor (CDAi), which enables oral AZA to achieve systemic AUC similar to that of parenteral (subcutaneous) AZA. ASTX030 successfully achieved the primary endpoint of PK equivalence versus SC AZA based on total cycle AUC. Dose combinations were well tolerated and safety profile was similar to SC AZA, with no unique AEs. Phase 1B dose expansion for ASTX030 at recommended dose combination of 144 mg AZA with 20 mg CED will confirm PK equivalence for this dose level."

PK/PD data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. (PubMed, J Oncol Pharm Pract) - "Treatment with oral HMAs has the potential to improve quality of life, treatment adherence, and disease outcomes versus parenteral HMAs. Better education of multidisciplinary teams on the factors affecting HMA treatment selection may help to improve treatment outcomes in patients with MDS or AML."

Journal • PK/PD data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Taiho Oncology and Astex Pharmaceuticals Announce Data Presentations at the 65th ASH Annual Meeting (Astex Press Release) - "Taiho Oncology Inc. and Astex Pharmaceuticals, Inc. announced today details of studies to be presented at the 65th American Society of Hematology (ASH) Annual Meeting, to be held Dec. 9-12, 2023, in San Diego. Among these data are the results of a real-world study of oral decitabine and cedazuridine in patients with myelodysplastic syndromes (MDS), which will be featured in an oral presentation."

Clinical data • Real-world • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML (clinicaltrials.gov) - P2/3 | N=317 | Recruiting | Sponsor: Astex Pharmaceuticals, Inc. | Trial completion date: Apr 2024 ➔ Apr 2026 | Trial primary completion date: Apr 2024 ➔ Dec 2025

Combination therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Jan 2024 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Servier Bolsters Position as the Leader in Mutant IDH Inhibition with Positive New IDH1-Mutated Acute Myeloid Leukemia Data at ASCO (Servier Press Release) - "'With a five-year survival rate of approximately 29.5%, the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. Moreover, for up to 10 percent of AML patients, the IDH1-mutation contributes to the development of acute leukemia,' said Eytan Stein, MD...'For these reasons, identifying the characteristics of patients who may respond to targeted therapy for the IDH1-mutation through molecular testing is of significant importance for treatment strategy and prognosis.'"

Media quote

How can outcomes be improved in patients with molecularly-defined high-risk AML? (YouTube) - "During the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, the AML Hub was pleased to speak to Alice Mims...We asked, How can outcomes be improved in patients with molecularly-defined high-risk acute myeloid leukemia (AML)?"

Video

Expert Perspectives on Current and Emerging Therapies for AML : Episode 12: Novel Venetoclax-Based Regimens in Patients With AML Unfit for Intensive Chemotherapy (OncLive) - "Margaret T. Kasner, MD:Let me let make 1 quick comment about azacitidine-IDH mutations because it fits here too....Hetty E. Carraway, MD:I want to highlight that these single IDH inhibitors can be well tolerated. You need to be more patient, and responses do happen in older patients. The data are provocative and nice for some of our patients who otherwise wouldn't be able to tolerate something like azacitidine-venetoclax."

Video

Expert Perspectives on Current and Emerging Therapies for AML : Episode 11: Frontline Treatment in Patients With IDH-Mutated AML Unfit for Intensive Chemotherapy (OncLive) - "In the setting of IDH-mutated AML, panelists consider optimal treatment options in patients unfit for intensive chemotherapy....Hetty E. Carraway, MD:For many of our patients, we aren't getting that IDH mutation back soon enough. If we're going to use an azacitidine-venetoclax approach, we'll launch into that. Often that's happening in the region before those patients even come to us, and that's where some of the rub is."

Video

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Jul 2022 ➔ Jan 2024 | Trial primary completion date: Mar 2022 ➔ Oct 2023

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology