cedazuridine/azacitidine (ASTX030) / Otsuka - LARVOL DELTA

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 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 • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

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

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 • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

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

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 2023 ➔ Apr 2024 | Trial primary completion date: Apr 2023 ➔ Apr 2024

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

[VIRTUAL] Industry Supported Session 04- Not Included in main event CME/CPD Credit (MDS 2021) - "We will review the clinical data which led to the approval of oral decitabine and cedazuridine, including new overall survival data from the ASCERTAIN Phase 3 clinical trial, and will outline how Astex is continuing to develop the product to address the emerging new standards of care for the treatment of AML and MDS. We will also outline some of the other products being developed by Astex for the treatment of hematological malignancies and solid tumors, including an oral azacitidine and cedazuridine product which uses the same fixed dose combination concept as oral decitabine and cedazuridine to deliver an equivalent pharmacokinetic exposure to IV or SC azacitidine."

CME • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome

Update on the management of patients with MPNs in transformation (YouTube) - "Dr Verstovsek reports that there are no effective therapies for patients with MPNs in transformation and comments on how improved understanding of the biology of MPN transformation has identified hypomethylating agents, such as azacitidine and decitabine, as potential agents for the treatment of patients with MPNs in transformation. Dr Verstovsek also talks of the benefits of genomic testing. This interview took place at the Texas MPN Workshop: Second Annual Workshop and Meeting in 2021."

Interview • Video

TOP ASCO 2021: Hematology [Google translation] (YouTube) - "Dr. Efreén Horacio Montaño Figueroa...together with Dr. Anna María Sureda Balari...tell us about the highlights in hematology presented at ASCO 2021..."

Video

A Conversation with the Investigators: Acute Myeloid Leukemia and Myelodysplastic Syndromes (Research To Practice) - "Management of Acute Myeloid Leukemia (AML) in Older Patients or Those Ineligible for Intensive Chemotherapy....Management Strategies for MDS."

CME

Using Available Evidence and Guidelines for Managing an Evolving AML Treatment Paradigm (Clinical Care Solutions) - "February 24, 2021, 12:15 - 12:45 PM ET; Summarize the NCCN Guidelines Recommendations for the treatment of AML in patients 60 years of age or older, Describe the results of the BRIGHT AML 1003, VIALE-A, and CPX-351 clinical trials in the treatment of patients with AML....Discuss the use of oral azacitidine, as well as gemtuzumab ozogamicin, based on the results of various recent clinical trials."

Live event

The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era. (PubMed, Expert Rev Anticancer Ther) - "Following the approval of the cedazuridine/decitabine combination, ASTX727, as well as development of an oral formulation of azacitidine, CC-486, in the USA in 2020, these agents could gradually replace their injectable counterparts...However, their FDA-approved indications at this point are narrow and efficacy needs to be shown in clinical trials before considering use beyond the approved indications. Areas of special interest include; identification of predictive biomarkers for clinical benefit, post-transplant maintenance therapy, and potential combination therapies with other oral agents such as venetoclax, IDH and FLT3 inhibitors."

Clinical • Journal • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FLT3

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Otsuka Pharmaceutical Co., Ltd.

Clinical • New P1 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology