Inqovi (decitabine/cedazuridine) / Otsuka - LARVOL DELTA

Patient experience sub-study of a randomised UK multicentre Phase 2 trial of ASTX727 versus hydroxycarbamide/best supportive care in myelodysplastic (MDS)/myeloproliferative (MPN) overlap syndromes (AMMO) (ASH 2025) - "Results highlight variation in support/information needs, with desire for more robust communication, especially around personal trial completion/next steps, a recurrent theme. Other areas identified as key to optimising patient experience included coping/support mechanisms and financial toxicities; reaffirming the importance of trial sponsors making provision for cost reimbursement."

Clinical • P2 data • Cardiovascular • Hematological Malignancies • Infectious Disease • Mood Disorders • Myelodysplastic Syndrome

Risk of relapse and mortality after non-myeloablative allogeneic stem cell transplant for Acute Myeloid Leukemia and myelodysplastic syndrome after fludarabine, cyclophosphamide, and 200 centigray total body irradiation with gvhd prophylaxis using post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil: Impact of maintenance chemotherapy (ASH 2025) - "Oral HMA agents were decitabine/cedazuridine (dec-c) 3d/28-day cycle, and oral azacitidine (Oral-Aza) for 14 days per 28-day cycle...A total of 32 (31%) patients received post-HSCT maintenance chemotherapy: infusional HMA (n=2), recombinant-Granulocyte Colony Stimulating Factor (rhGCSF)/decitabine (n=2), gilteritinib (n=7), dec-c (n=9), oral-aza (2), and venetoclax/Azacitidine (n=8)... NMA conditioning with Flu/Cy/2Gy TBI yields low NRM. Post-transplant maintenance therapy, particularly with HMAs and targeted agents, is associated with reduced relapse in intermediate-risk and adverse-risk TP53 wt AML and MDS. However, outcomes remain poor for patients with TP53 mu t AML and MDS, indicating an urgent need for alternative or intensified maintenance strategies in these high-risk groups."

Clinical • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Chronic Myelomonocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Transplantation • FLT3 • TP53

Oral decitabine-cedazuridine versus parenteral hypomethylating agents in treatment-Naïve TP53-mutated Myelodysplastic Syndromes (ASH 2025) - "Pts were grouped by initial therapy: Dec-C or pHMA (azacitidine or decitabine)...Venetoclax was used with HMA in 22 pts (Dec-C, n=4; pHMA, n=18), and those pts were excluded from further analyses...The lower incidence of febrile neutropenia with Dec-C may reflect variability in initial dosing schedules. Although limited by small sample size and retrospective design, these real-world findings can inform clinical use of Dec-C as a potentially effective frontline option for patients with m TP53 -MDS."

Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

Addition of venetoclax to hypomethylating agent offers limited incremental benefit for patients with treatment-naïve TP53-mutated myelodysplastic syndromes (ASH 2025) - "The HMA used included azacitidine (HMA: n=18; HMA-Ven: n=11), decitabine (HMA: n=15; HMA-Ven: n=7), and decitabine-cedazuridine (HMA: n=21; HMA-Ven: n=4). However, pts with increased blasts and m TP53 appeared to respond better to HMA-Ven. Allo-SCT should be considered for all eligible pts with m TP53 -MDS, as it remains the single independent predictor of improved OS in this subgroup."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • TP53

Molecular correlates of response and survival with venetoclax plus hypomethylating agent in treatment-Naïve high-risk myelodysplastic syndrome (ASH 2025) - "HMA backbones included azacitidine (75 mg/m² IV/SC, days 1–7), IV decitabine (20 mg/m², days 1–5), or oral decitabine-cedazuridine (35 mg/100 mg, days 1–5). However, we observed trends suggesting prognostic relevance for specific mutations ( TP53 , ASXL1 , RAS vs. RUNX1 , TET2 , DNMT3A ). These findings highlight the utility of Ven-HMA as a bridge to transplant, frequent need for dose modification, and underscore the complex interplay of molecular genetics in determining outcomes, which warrants validation in larger studies."

Tumor mutational burden • Hematological Malignancies • Myelodysplastic Syndrome • ASXL1 • DNMT3A • KRAS • NRAS • RUNX1 • SF3B1 • SRSF2 • TET2 • TMB • U2AF1 • ZRSR2

Rhabdomyolysis in patients taking isocitrate dehydrogenase inhibitors for R/R Acute Myeloid Leukemia (ASH 2025) - "She was started on treatment with azacitidine, venetoclax, and magrolimab and achieved MRD-negative CR after cycle 1, then went on to complete 6 cycles of therapy, followed by 4 cycles of maintenance therapy with combination decitabine/cedazuridine and venetoclax prior to relapse. She was then treated with combination decitabine/cedazuridine, venetoclax, and ivosidenib...Azacitidine was discontinued after C33, at which time she continued on enasidenib monotherapy...She was on a stable dose of atorvastatin at the time of this event and had recently started azithromycin for symptoms of upper respiratory tract infection...al 2015). We hypothesize that rhabdomyolysis observed with IDH inhibitors may reflect a convergence of metabolic stressors, particularly in susceptible populations such as elderly patients with low muscle mass, and those on concomitant statins."

Clinical • Acute Myelogenous Leukemia • Brain Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Musculoskeletal Pain • Myelodysplastic Syndrome • Respiratory Diseases • Solid Tumor • Thrombocytopenia • IDH1 • IDH2

A multiarm phase 1b study of personalized oral maintenance therapy with decitabine/cedazuridine (ASTX727) plus physician's choice of venetoclax, gilteritinib, enasidenib, or ivosidenib in Acute Myeloid Leukemia (ASH 2025) - P1 | "Pts were required to have received at least 2 courses of intensive chemotherapy(intermediate to high-dose cytarabine-based) or 3 courses of low-intensity therapy (HMA or low-dosecytarabine-based) prior to enrollment. Personalized fully oral maintenance therapy is feasible in AML. Myelosuppression andinfections were the most common adverse events. Further enrollment and follow-up is needed toevaluate efficacy."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • TP53

Phase I/II study of decitabine/cedazuridine (ASXT727), venetoclax, and gilteritinib for patients with FLT3-mutated Acute Myeloid Leukemia or high-risk myelodysplastic syndrome (ASH 2025) - "The triplettherapy with azacitidine, venetoclax (VEN), and gilteritinib (GILT) has shown encouraging survival in FLT3-mutated AML. The combination of ASTX727, VEN and GILT is feasible but associated with myelosuppression,necessitating dose reductions."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • DNMT3A • FLT3 • KRAS • NPM1 • NRAS

Low-dose oral decitabine and cedazuridine among patients with low-risk myelodysplastic syndromes (ASH 2025) - P1/2 | "Background : Parenteral DNA methyltransferase inhibitors (DNMTi) such as azacitidine and decitabine(DEC), including an attenuated 3-day regimen, are recommended in the NCCN Guidelines for patients(pts) with lower-risk myelodysplastic syndromes (LR-MDS) with clinically significant cytopenias. LD oral DEC-C demonstrated comparable clinical benefit to SD oral DEC-C, with improvedsafety and tolerability, including fewer dose modifications and less severe myelosuppression. Thesefindings support LD DEC-C as a potential optimal regimen for pts with LR-MDS.Clinical trial registration: NCT03502668"

Clinical • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia

Trial in progress: A phase I study evaluating the safety of cirtuvivint (CIRT) as monotherapy and in combination with ASTX727 in patients with myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML) (ASH 2025) - P1 | "Outcomes afterresistance to venetoclax-based therapy are particularly poor with a median OS of 2.5 monthsindependent of the type of salvage therapy used (Maiti et al., Haematologica 2020). ConclusionsThis phase I trial will establish the safety and RP2D for CIRT as monotherapy in R/R AML or R/R MDS(cohort I and II) and in combination with ASTX727 for untreated higher-risk MDS (cohort III). The trial isactively recruiting and aims to inform future phase II studies."

Clinical • Combination therapy • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Solid Tumor • XIAP

A randomized Phase II trial of ASTX727 and venetoclax with or without enasidenib for newly diagnosed older adults with IDH2 mutant Acute Myeloid Leukemia: A myelomatch substudy (MM1OA-S03) (ASH 2025) - P2 | "In IDH1 mutant AML, a phase 1btrial of the combination of the IDH1 inhibitor ivosidenib with venetoclax and azacitidine resulted in anoverall response rate of 94% with MRD negativity achieved in 77%, without any patients discontinuingtherapy due to intolerance. The study wasactivated on April 1, 2025 and is expected to continue until October 2027. Funding: Funding: NIH/NCI grants U10CA180888, U10CA180819"

Clinical • P2 data • Acute Myelogenous Leukemia • Multiple Myeloma • IDH1 • IDH2

Thioguanine and decitabine can overcome hypomethylating agent resistance in patients with advanced myeloid malignancies (ASH 2025) - "Background : Despite active therapies such as hypomethylating agents (HMA) and venetoclax advancedmyeloid malignancies, outcomes in relapsed/refractory (R/R) disease or secondary acute myeloidleukemia (AML) remain poor. 6TG/DEC is a clinically active regimen in high-risk and R/R AML with a 30% ORR andfavorable survival outcomes compared to historical controls. Single-cell proteomic data reveal immune-modulatory mechanisms that may underlie therapeutic response, offering a novel lens into resistancebiology. Taken together, this combination remains a viable therapeutic option for elderly and unfitpatients with high-risk and R/R AML who cannot tolerate intensive chemotherapy."

Clinical • Metastases • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • B2M • CD36 • SCARB1

Trial in progress - a randomized study of ASTX727 with or without Iadademstat in accelerated/blast-phase myeloproliferative neoplasms (ASH 2025) - P2 | "Outcomes were similar in patients treated with intensivechemotherapy, DNA methyltransferase inhibitor (DNMTi) + venetoclax-based therapy, and other DNMTi-based approaches (Patel et al, Blood Adv 2024)...The oral LSD1 inhibitor iadademstat has been studiedin combination with the DNMTi azacitidine in de novo acute myeloid leukemia (AML) in the context of thePhase II ALICE study; the complete remission (CR)/complete remission with incomplete count recovery(CRi) rate was 52%...Exclusion criteria of note include IDH1-mutatedMPN-BP (due to the availability of ivosidenib as an approved frontline therapy).The dose escalation phase will follow a 3+3 design...Secondary endpoints include event-free survival, overall survival, and percentage of patients that go onto allogeneic stem celltransplantation. Exploratory endpoints include concordance of response between EuropeanLeukemiaNet (ELN) 2022 response criteria (Dohner et al, Blood 2022) and 2012 MPN-BP criteria,assessment of..."

Clinical • Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • ASXL1 • IDH1 • IDH2 • TP53

ASTX727 delivers superior response rates and associated survival benefit versus hydroxycarbamide/best supportive care in CMML and other MDS/MPN overlap syndromes: First results from the Phase 2 UK multicenter randomized ammo trial (ASH 2025) - "Rapid recruitment(6mo early) and high retention showcases feasibility/appetite for RCTs in this challenging group.Extending access beyond CMML AMMO also showcases HMA efficacy across related biological entities.The 53% ORR is in keeping with that expected for HMA monotherapy and almost double that for HC/BSC.Toxicity was higher, but acceptable and in line with prior ASTX727 trials. Crucially this did not negate itsefficacy advantage, translating into significantly longer PFS, TFS and OS: the first randomized survivalbenefit demonstrated in MDS/MPN for ~30y and supporting ASTX727 as a new SoC for advancedMDS/MPN."

Clinical • P2 data • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Respiratory Diseases • Thrombocytopenia

Trends in overall survival in MDS from 2000–2022: Have therapeutic advances made a difference? (ASH 2025) - "Over time, treatment for MDS has evolved from supportive care tohypomethylators (azacitidine, decitabine, decitabine/cedazuridine), followed by newer agents such asluspatercept. The effectiveness ofhypomethylating agents and newer agents like luspatercept appears limited, particularly among higher-risk patients. Future efforts should focus on refining risk stratification, identifying gender specific riskfactors and clinical approach, expanding access to clinical trials, and exploring treatment options such asnovel targets for antibodies or T cell modulation therapies to ensure improved survival in near future."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Thrombocytopenia

Chronic myelomonocytic leukemia: Clinical outcomes from clinical trials submitted to the FDA over the past 25 years (ASH 2025) - "Due to its rarity, clinical research inCMML has been limited, with current therapeutic approvals restricted to only three hypomethylatingagents (HMAs): azacitidine, decitabine, and decitabine/cedazuridine...To address these gaps, this study aims to evaluate overall survival (OS)outcomes and response rates across different treatment modalities and across CMML subtypes.MethodsWe searched for phase 2 and 3 trials including patients with CMML submitted to FDA as part of New DrugApplications and Investigational New Drug Applications for the treatment of MDS between 2000 and2025...We identified 10 trials evaluating 5 investigational agents for MDS treatment that included a total of 196patients with CMML. These 196 patients were categorized into three treatment groups: HMAmonotherapy (n=104), HMA combination therapy (n=63) and control (conventional care regimen orsupportive care, n=29). The study population had a median age of 70 years, was 69% male, and included85% White, 12%..."

Clinical • Clinical data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Translational investigation of tolinapant (ASTX660) in Acute Myeloid Leukemia using integrated clinical, bioinformatic, and pharmacological approaches (ASH 2025) - P1 | "Inacute myeloid leukemia (AML), a study evaluating tolinapant as a single agent and in combination withcedazuridine (ASTX727) in patients with relapsed/refractory AML was prematurely terminated(NCT04155580)...Although tolinapant displayed limited single-agent activity, its combination with venetoclax yieldedsynergistic or additive cytotoxic effects in resistant models. These findings support further investigationof tolinapant-based combination therapies, particularly in biomarker-defined AML subsets. Supported byFAPESP, CAPES, and CNPq."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • T Cell Non-Hodgkin Lymphoma • ANXA5 • BIRC2 • BIRC3 • XIAP

A retrospective analysis of outcomes of high-risk myelodysplastic syndrome patients treated with upfront decitabine/cedazuridine versus hypomethylating agents with venetoclax utilizing real-world data (ASH 2025) - "Our matched cohort analysis of front-line use of DEC-C was associated with better OS and lower risk ofprogression to AML compared to VEN/HMA in HR-MDS patients. Further prospective studies arewarranted to confirm such benefits associated with this new oral agent in the treatment of HR-MDSpatients."

Real-world • Real-world evidence • Retrospective data • Acute Myelogenous Leukemia • Alzheimer's Disease • Chronic Kidney Disease • Chronic Myelomonocytic Leukemia • CNS Disorders • Congestive Heart Failure • Dementia • Diabetes • Heart Failure • Hematological Malignancies • Hepatology • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myocardial Infarction • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases

Oral decitabine/cedazuridine in combination with venetoclax in treatment-naïve high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia: Updates of a Phase 1/2 clinical trial (ASH 2025) - P1/2 | "The combination of DEC-C with Ven is a feasible combination, well-tolerated and with a highresponse and HSCT rate in high-risk MDS and CMML."

Clinical • Combination therapy • IO biomarker • P1/2 data • Alzheimer's Disease • Atypical Chronic Myeloid Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • CNS Disorders • Dementia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Pneumonia • Respiratory Diseases • Septic Shock • ASXL1 • RUNX1 • SRSF2 • TET2 • TP53

Phase II Study of the all-oral combination of revumenib (SNDX-5613) with decitabine/cedazuridine (ASTX727) and venetoclax (SAVE) in newly diagnosed AML (ASH 2025) - P1/2 | "ConclusionSAVE, an all-oral combination, shows promising activity in older adults with ND NPM1m or KMT2Ar AMLwho are ineligible for intensive chemotherapy. Ongoing enrollment and longer follow-up are required toestablish the durability of response."

P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Pulmonary Disease • Respiratory Diseases • FLT3 • KMT2A • KRAS • MEN1 • NPM1 • NRAS • NUP98

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=53 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

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

ASCERTAIN-V: Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1/2 | N=101 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Durable Transfusion Independence in Lower-Risk Myelodysplastic Syndrome (LR-MDS) Is Associated with Better Survival: A Population Level Analysis Based on a Large US Health Insurance Claims Database (ASH 2023) - "Lines of treatment were determined based on claims for MDS treatments contained in the database: erythropoietin stimulating agents (ESAs; darbepoetin, epoetin alfa), hypomethylating agents (HMAs; azacitidine, decitabine, decitabine-cedazuridine), lenalidomide, luspatercept, eltrombopag, and cyclosporine. Among patients with LR-MDS, 35% and 49% were RBC-TD before 1L and 2L of therapy, respectively. Achievement of TI was associated with improved survival, suggesting that RBC-TD is a modifiable predictor of clinical outcomes in LR-MDS. Despite the currently available therapies, RBC-TD after any line of therapy is associated with poorer outcomes."

Claims database • Clinical • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology

Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma (clinicaltrials.gov) - P1/2 | N=8 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial primary completion date: Oct 2025 ➔ Aug 2026

Checkpoint inhibition • IO biomarker • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • CD4

Venetoclax/FluBu2 RIC transplant followed by all-oral venetoclax/decitabine maintenance for poor risk MDS/AML. (PubMed, Blood Adv) - P1 | "To improve the tolerability of post-transplant maintenance and outcomes despite poor risk disease genetics, we conducted a phase 1 study of venetoclax/FluBu2 RIC transplantation with tacrolimus/methotrexate GVHD prophylaxis followed by all-oral venetoclax/decitabine-cedazuridine (ven/dec-c) maintenance in poor-risk MDS/AML patients (N=30). PROs assessed in first 6-months of maintenance were stable except for emotional function, which improved (P=0.008). Trial is registered at clinicaltrials.gov/NCT03613532."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Transplantation • TP53