Inqovi (decitabine/cedazuridine) / Otsuka - LARVOL DELTA

STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov) - P2 | N=39 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.

Trial termination • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Sanjay Mohan | N=51 ➔ 1 | Trial completion date: Mar 2029 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ Sep 2024; Study was terminated early due to lack of accrual and loss of funding.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Inqovi Maintenance Therapy in Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2024 ➔ Nov 2026

Enrollment closed • Trial completion date • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • HLA-B

An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 pts. (BASCO-MN 2025) - No abstract available

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Taiho Oncology and Taiho Pharmaceutical Announce U.S. FDA Acceptance of Supplemental New Drug Application for INQOVI in Combination with Venetoclax to Treat Patients with Acute Myeloid Leukemia (PRNewswire) - "Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd., announced today that the U.S. Food and Drug Administration (FDA) has accepted their supplemental new drug application (sNDA) for INQOVI (decitabine and cedazuridine) plus venetoclax as a treatment for adults with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy. The FDA assigned a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of February 25, 2026. The sNDA is supported by results from ASCERTAIN-V, a Phase 2b study of INQOVI plus venetoclax in 101 adult patients with newly diagnosed AML who were ineligible for intensive induction chemotherapy....The trial met its primary endpoint with a complete response (CR) rate of 46.5% (n=47)."

FDA filing • PDUFA • Acute Myelogenous Leukemia

PK/Efficacy Bridging Study of ASTX727 in Chinese Subjects With Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=72 | Active, not recruiting | Sponsor: Otsuka Beijing Research Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

CHART REVIEW STUDY ON DOSE MODIFICATIONS OF PATIENTS WITH MYELODYSPLASTIC SYNDROME TREATED WITH HYPOMETHYLATING AGENTS (EHA 2025) - "Background: Decitabine and cedazuridine (DEC-C), an oral hypomethylating agent (HMA), was approved in July 2020 in the U.S. for the treatment of adult patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia. DEC-C is the only oral HMA approved for MDS, whereas other HMAs, including decitabine (DEC) and azacitidine (AZA), are administered intravenously or subcutaneously... Delaying the start of a subsequent treatment cycle was the most common strategy used by providers to manage toxicity among MDS patients who received HMA regardless of route of administration, while dose reduction was less frequently utilized. Parenteral AZA appeared to have the highest frequency of dose modifications among the HMAs studied. These findings provide valuable insights into real-world practice for managing HMA therapy in MDS patients."

Clinical • Review • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A PHASE IB/2 TRIAL OF AN ALL-ORAL "TRIPLET" REGIMEN FOR IDH-MUTATED MYELOID MALIGNANCIES: DECITABINE/CEDAZURIDINE AND VENETOCLAX IN COMBINATION WITH IVOSIDENIB/ENASIDENIB (EHA 2025) - P1/2 | "An all-oral triplet regimen of DEC-C+VEN+IVO/ENA demonstrated an impressive CRc rate in both ND and R/R pts with IDH mutant myeloid neoplasms with no new safety signals."

Combination therapy • Acute Myelogenous Leukemia • Hepatology • Infectious Disease • Myelodysplastic Syndrome • IDH1 • IDH2 • TP53

ALL-ORAL DECITABINE-CEDAZURIDINE (DEC-C) + VENETOCLAX (VEN) IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) INELIGIBLE FOR INDUCTION CHEMOTHERAPY: PHASE 1/2 CLINICAL TRIAL RESULTS (EHA 2025) - P1/2 | "Background: In patients (pts) with AML aged ≥75 years or otherwise ineligible for induction chemotherapy (ICT), the combination of azacitidine (AZA) with the Bcl-2 inhibitor VEN is approved based on the VIALE-A trial (complete remission [CR] rate, 36.7%; median overall survival [mOS], 14.7 months); intravenous (IV) decitabine (DEC) + VEN is also approved in this setting. The all-oral regimen of DEC-C + VEN resulted in comparable safety, response, and survival rates to parenteral AZA + VEN in pts with newly diagnosed AML ineligible for ICT. Compared with standard dosing, early BM examination and subsequent dose reductions in DEC-C and/or VEN during post-remission treatment cycles were associated with improved long-term outcomes and tolerability. These data underscore the importance of regimen optimization and suggest a practice-changing role for oral DEC-C + VEN in this pt population with high unmet need."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology

Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher-Risk Myelodysplastic Syndrome (MDS) With IDH2 Mutation (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2025 ➔ Jun 2025

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Efficacy and safety of oral decitabine/cedazuridine in the chronic myelomonocytic leukaemia subpopulations from phase 2 and 3 studies. (PubMed, Br J Haematol) - "Median overall and transformation-free survival were 35.7 and 28.3 months, respectively, and the safety profile was similar to that previously reported for decitabine. This analysis described the use of decitabine/cedazuridine in CMML from consecutive, prospective, randomised trials and illustrated a median survival of nearly 3 years."

Journal • P2 data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: OHSU Knight Cancer Institute | Recruiting ➔ Suspended

Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

A Study to Find the Highest Dose of Cedazuridine and Decitabine Combination With Filgrastim as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With High-Risk Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=47 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Testing the Anti-cancer Drug, Cirtuvivint, and Its Combination With ASTX727 to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Outcomes of post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance therapy in FLT3-mutated, IDH-mutated, or high relapse-risk myeloid malignancies: A single-center experience. (ASCO 2025) - "Eight patients with FLT3-ITD/TKD mutations received gilteritinib starting at 40 mg with 22% reaching the goal dose of 120 mg...Quizartinib was started on 1 patient at 17.7 mg with a plan to increase to 53 mg...Ivosidenib was started at 500 mg in 2 patients with IDH1 mutations...Enasidenib was started at 100 mg in 8 patients with IDH2 mutations with none needing dose reductions...Fourteen patients with high-risk disease received decitabine at 10mg/m2 for 5 days (n= 12) or oral decitabine/cedazuridine 35/100mg/day for 2 days (n= 2) every 6 weeks, aiming for 6-9 cycles... Post-HSCT maintenance therapy, with small molecule inhibitors in AML with FLT3/IDH mutations and with decitabine in high-relapse risk AML/HR-MDS, appears well tolerated with excellent survival indices, especially in FLT3 and IDH mutated cohorts. This warrants further investigation into optimizing post-HSCT maintenance strategies."

Clinical • Acute Kidney Injury • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Influenza • Leukemia • Myelodysplastic Syndrome • Nephrology • Neutropenia • Oncology • Pain • Pneumonia • Renal Disease • Respiratory Diseases • Transplantation • FLT3 • IDH1 • IDH2

A phase I/Ib study of olaparib and ASTX727 in BRCA 1/2- and HRD-mutated tumors. (ASCO 2025) - P1 | "Individuals with a prior or concurrent malignancy are eligible, however participants diagnosed with MDS or AML are excluded from the study. Trial Status: The study is ongoing and 4 patients have been enrolled to date."

P1 data • Acute Myelogenous Leukemia • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • CHEK2 • HRD • PALB2 • RAD51

An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 pts. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT04657081 Background: In pts with AML aged ≥75 years and ineligible for induction chemotherapy, the combination of the Bcl-2 inhibitor VEN plus azacitidine (AZA) was approved based on the Phase 3 VIALE-A trial (complete remission [CR] rate, 36.7%; median CR duration, 17.5 months; median overall survival [OS], 14.7 months). The all-oral regimen of DEC-C plus VEN resulted in comparable safety, response, and survival rates to parenteral AZA plus VEN in pts with newly diagnosed AML ineligible for intensive induction chemotherapy. These data support the potential use of DEC-C plus VEN as a treatment option for these pts."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology

Phase II trial of 10-day ASTX727 (decitabine/cedazuridine) in combination with venetoclax for relapsed or refractory acute myeloid leukemia. (ASCO 2025) - P2 | "The 10-day ASTX727-VEN combination showed safety profile comparable to other HMA-VEN regimens in salvage setting. TP53 wild type, VEN-naïve pts and those who could be bridged to SCT had better outcomes. Novel therapies are needed to improve outcomes in R/R AML."

Combination therapy • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • TP53

The phase II NIBIT-ML1 study of nivolumab plus ipilimumab and ASTX727 or nivolumab plus ipilimumab in PD-1 resistant metastatic melanoma: Tumor methylation landscape and correlation with clinical outcomes. (ASCO 2025) - P2 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT04250246 Background: In the NIBIT Foundation-sponsored phase Ib NIBIT-M4 study, we firstly showed that the hypomethylating agent (HMA) guadecitabine (guade), a prodrug of decitabine (D), followed by ipilimumab (I) was safe with promising clinical and immunologic activity in cutaneous metastatic melanoma (MM) patients (pts) (Di Giacomo, Clin Cancer Res 2019; Noviello, Nat Commun 2023). Treatment with ASTX727 plus I+N is feasible and has meaningful clinical and immunologic activity in PD-1 refractory MM pts."

Clinical • Clinical data • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms? (PubMed, Curr Opin Oncol) - "Epigenetic modifications play a crucial role in NENs, influencing tumour progression, therapy resistance, and SSTR2 expression. Epigenetic priming with DNA methyltransferase and HDAC inhibitors can enhance SSTR2 expression, improving the efficacy of PRRT in NENs. The LANTana study and other trials are investigating whether epigenetic-targeting approaches can be integrated into NEN treatment to optimize PRRT and overcome therapeutic limitations."

Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR2

Nodal Mature Plasmacytoid Dendritic Cell Proliferation in a Patient With Chronic Myelomonocytic Leukemia: A Diagnostic Mimic of Blastic Plasmacytoid Dendritic Cell Neoplasm. (PubMed, J Investig Med High Impact Case Rep) - "The patient was initially treated with hydroxyurea, later transitioned to decitabine/cedazuridine (Inqovi) for disease progression. Recognizing MPDCP in unusual locations is critical for accurate diagnosis and prognostication. Further studies are warranted to clarify its molecular pathogenesis and potential as a biomarker of disease evolution in CMML and related disorders."

Journal • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Langerhans Cell Histiocytosis • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • T Cell Non-Hodgkin Lymphoma • ASXL1 • CD123 • CD4 • CLEC4C • GZMB • IL3RA • NCAM1

Eltanexor (KPT-8602) With Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=3 | Completed | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Completed | N=80 ➔ 3 | Trial completion date: Jul 2027 ➔ Mar 2025 | Trial primary completion date: Apr 2027 ➔ Mar 2025

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

Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=93 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2025 ➔ May 2025

Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

MPD/MDS (MDS 2025) - "This has led to the use of parenteral azanucleuosides decitabine and azacitidine, and the oral agent, decitabine/cedazuridine in the United States, for CMML...Efforts to expand the use of azanucleosides in MP-CMML in Europe led to the DACOTA phase III study which compared decitabine to hydroxyurea for patients with MP-CMML...ABNL MARRO-001 is the first ABNLMARRO study which includes randomly assigns patients to arms of novel therapies together with the DNA methyltransferase, ASTX727 (DEC-C/decitabine-cedazuridine). ABNLMARRO 002 is due to open in late 2025, and additional novel therapies will be entering ABNLMARRO in efforts to develop the first modern therapies approved in US and EU, specifically for CMML."

Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Oral regimen of decitabine and cedazuridine plus venetoclax in newly diagnosed AML (PRNewswire) - P1/2 | N=101 | NCT04657081 | Sponsor: Taiho Oncology, Inc. | "Taiho Oncology...announced new data to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting....This Phase 1/2 trial evaluated the regimen of decitabine and cedazuridine plus venetoclax in 101 patients with newly diagnosed AML who were ineligible for first-line induction chemotherapy. Complete remission (CR) and CR with incomplete hematologic recovery rates were 46.5% and 63.4%, respectively. Median time to CR was 2.4 months. Median CR duration was not reached; among patients who achieved CR, 80% maintained that status at 6 months and 75.3% at 12 months. Median OS was 15.5 months. Ninety-eight percent of patients reported treatment-emergent adverse events of grade 3 or lower, most commonly febrile neutropenia (49.5%), anemia (38.6%) and neutropenia (35.6%). The 30- and 60-day mortality rates were 3% and 9%, respectively."

P1 data • Acute Myelogenous Leukemia