Inqovi (decitabine/cedazuridine) / Otsuka, Taiho - LARVOL DELTA

The All-Oral Combination of Revumenib, Decitabine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia (SAVE). (PubMed, J Clin Oncol) - "This combination was associated with high response rates and durable remissions, with an acceptable safety, in heavily pretreated patients with AML harboring alterations susceptible to menin inhibition."

IO biomarker • Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

Concurrent Remission of Therapy-Related Acute Myeloid Leukemia and IgG-λ MGUS During Oral Decitabine-Cedazuridine: A Case Report. (PubMed, Hematol Rep) - "Such treatments include those containing venetoclax, an easy-to-use all-oral form of decitabine-cedazuridine (DEC-C), which is now available and approved for AML in addition to standard parenteral DNA methyltransferase inhibitors, which have been commonly used in routine clinical practice for about two decades in patients unsuitable for intensive chemotherapy (IC). Maintenance therapy with oral DEC-C is ongoing for 18 months after achieving CRi, without any signs of toxicity or infection. This report describes the first anecdotal case of t-AML responding to DEC-C with concomitant clearance of the paraprotein associated with MGUS."

Journal • Acute Myelogenous Leukemia • Breast Cancer • Gene Therapies • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Solid Tumor

Survival and Toxicity Outcomes With Hypomethylating Agent Plus Venetoclax vs Hypomethylating Agent Alone in Higher-Risk Myelodysplastic Syndrome: A Propensity-Matched Retrospective Cohort Study (SOHO 2026) - "Patients/Participants: Adults with HR-MDS receiving azacitidine, decitabine, or decitabine-cedazuridine. In this propensity score–matched real-world cohort of HR-MDS patients, HMA plus venetoclax was not associated with improved survival compared with HMA alone and carried higher mortality and infectious/myelosuppressive toxicity across all three time horizons. These findings support careful patient selection and prospective validation before broader adoption of this combination in HR-MDS."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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

PHASE 1/2 STUDY OF THE ALL-ORAL COMBINATION OF REVUMENIB (SNDX-5613) WITH DECITABINE/CEDAZURIDINE (ASTX727) AND VENETOCLAX (SAVE) IN RELAPSED/REFRACTORY AML (EHA 2026) - P1/2 | "ASTX727 (35/100 mg) was given PO on days 1–5, venetoclax 400 mg PO on days 1–14, and revumenib 113 mg (DL0) or 163 mg (DL1) PO Q12h on days 1–28 with posaconazole or voriconazole prophylaxis. Summary/Conclusion The all-oral combination of revumenib , venetoclax, and decitabine y ields high remission rates in R/R AML with KMT2Ar , NPM1mt , or NUP98r , with durable responses in patients achieving deep remission. Fig.1: Duration of response by genotype"

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Respiratory Diseases • Thrombocytopenia • BCL2 • KMT2A • NUP98

PHASE 1/2 STUDY OF ORAL DECITABINE/CEDAZURIDINE IN COMBINATION WITH VENETOCLAX IN TREATMENT-NAÏVE HIGHER-RISK MYELODYSPLASTIC SYNDROMES OR CHRONIC MYELOMONOCYTIC LEUKEMIA (EHA 2023) - P1/2 | "The combination of ASTX727 plus venetoclax is a promising, fully oral combination that is well-tolerated and demonstrates a high response rate in higher-risk MDS decitabine, Myelodysplastic syndrome, Venetoclax, Oral"

Combination therapy • IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Dermatology • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Transplantation • ASXL1 • RUNX1 • SRSF2 • TET2 • TP53

Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Varun Monga, MBBS | Recruiting ➔ Active, not recruiting

Enrollment closed • Myelodysplastic Syndrome • Oncology • BRCA • BRCA1 • BRCA2 • CHEK2

Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study. (PubMed, Lancet Haematol) - P2 | "ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia. Our findings should be confirmed in larger multicentric studies."

Journal • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • TP53

Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib in IDH Mutated Acute Myeloid Leukemia (ASH 2022) - "(Table 1) In the R/R cohort, 78% (n=11) patients had received prior treatment with either an HMA (azacitidine or decitabine), BCL2i and/or IDHi, with a median of 2 prior treatments...There were two patients with possible/probable differentiation syndrome which resolved with medical management (dexamethasone and diuresis)...AEs are anticipated and tolerable. Enrollment to this study is ongoing."

Combination therapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Hepatology • Mucositis • Myelodysplastic Syndrome • Neutropenia • Transplantation • IDH1

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

Long-term follow-up of oral decitabine/cedazuridine plus venetoclax for older or unfit patients with newly diagnosed acute myeloid leukemia. (PubMed, Haematologica) - "Response rates were higher in de novo AML, while survival outcomes were not statistically significant. These findings highlight the need for improved therapeutic strategies particularly in secondary AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 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

PHASE 1/2 STUDY OF ORAL DECITABINE/CEDAZURIDINE WITH VENETOCLAX AND GILTERITINIB IN PATIENTS WITH NEWLY DIAGNOSED AND RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2024) - P1/2 | "The combination of ASTX727 with VEN and GILT is a feasible fully oral combination for pts with FLT3mut AMLand MDS."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • DNMT3A • FLT3 • IDH2 • NPM1

Metronomic Decitabine-Cedazuridine and Venetoclax in R/R AML, HR-MDS, HR/AP MPN (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Virginia Commonwealth University | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology

Economic and organizational impact of oral versus intravenous and subcutaneous administration of hypomethylating agents in patients with acute myeloid leukemia not eligible for intensive chemotherapy in Spain. (PubMed, PLoS One) - "Hypomethylating agents (HMA) -intravenous (IV) decitabine and subcutaneous (SC) azacitidine- are standard therapeutic options but require frequent hospital visits and substantial healthcare resource use. Oral decitabine/cedazuridine (DEC-C) offers a therapeutically equivalent alternative that may reduce hospital resource burden and improve patient convenience...Oral administration substantially reduces direct non‑drug costs and frees hospital capacity, offering meaningful organizational efficiencies and contributing to the sustainability of AML care within a resource‑constrained health system. These findings reinforce the value of integrating oral HMAs into clinical pathways."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

Baseline Protein-Energy Malnutrition Identifies a High-Risk Phenotype in HMA-Treated Myelodysplastic Syndromes: A Propensity-Matched Real-World Analysis (SOHO 2026) - " Using the TriNetX US Collaborative Network (67 health care organizations), we identified patients with MDS (ICD-10 code D46) receiving azacitidine, decitabine, or decitabine-cedazuridine. Baseline PEM identifies a high-risk phenotype among patients with MDS initiating HMA therapy, marked by early mortality, hospitalization, infection, and frailty-related complications. Nutritional assessment before HMA initiation may complement established risk stratification and guide supportive care interventions. ICD-10: International Classification of Diseases, Tenth Revision."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study. (PubMed, Lancet Haematol) - P1/2 | "This early analysis suggests that the combination of oral decitabine plus cedazuridine with venetoclax for higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia is safe in most patients, with encouraging activity. Longer follow-up will be needed to confirm these data."

Journal • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • Thrombocytopenia • Transplantation

Weekly Hypomethylating Agent and Venetoclax Combination Therapy in Myeloid Neoplasms: A Real-World Single-Center Experience in an Older, High-Comorbidity Population (SOHO 2026) - "Most (17/19) received oral VEN plus decitabine/cedazuridine 35 mg/100 mg; one received subcutaneous decitabine 0.2 mg/kg, and one received IV decitabine 20 mg/m2. Weekly HMA/VEN, predominantly delivered as an all-oral regimen, demonstrated meaningful clinical activity with median OS of 11.7 months and median EFS of 10.4 months in an older, heavily pretreated, high-comorbidity cohort. Prospective evaluation in patients ineligible for standard HMA/VEN therapy is warranted. AML: acute myeloid leukemia; ASXL1: ASXL transcriptional regulator 1 gene; cCR: composite complete response; CMML: chronic myelomonocytic leukemia; CR: complete response; CRh: complete response with partial hematologic recovery; CYP3A4: cytochrome P450 3A4; ECOG PS: Eastern Cooperative Oncology Group performance status; EFS: event-free survival; ELN: European LeukemiaNet; FN: febrile neutropenia; HMA: hypomethylating agent; IDH2: isocitrate dehydrogenase (NADP(+)) 2 gene; IV: intravenous; MDS-IB:..."

Clinical • Combination therapy • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • IDH2 • RUNX1 • SRSF2 • TET2 • TP53

Early Results of the Phase I/II Study Investigating the All-Oral Combination of the Menin Inhibitor Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE) (ASH 2023) - P1/2 | "ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors, for antifungal prophylaxis). Early results indicate acceptable safety and high efficacy of this combination in R/R myeloid leukemias with either KMT2Ar or NPM1mt or NUP98r. This study is ongoing with plans to establish the recommended phase 2 dose and optimize delivery of this combination."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Pain • Renal Disease • Thrombocytopenia • Transplantation • KMT2A • NPM1 • NUP98

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

Comparative Efficacy and Safety of Oral Azacitidine (CC-486) Versus Injectable Hypomethylating Agents as Maintenance Therapy Following Allogeneic Haematopoietic Cell Transplantation in Myelodysplastic Neoplasms: A Systematic Review and Network Meta-Analysis (SOHO 2026) - P3 | " Twenty-five studies (n = 5847) were included—3 randomized controlled trials and 22 prospective or controlled retrospective cohorts-evaluating 5 treatment nodes: CC-486, injectable azacitidine, injectable decitabine, oral decitabine/cedazuridine, and observation. HMA maintenance post-alloHCT significantly improves survival and reduces relapse in MDS, with a favorable GVHD and NRM profile. CC-486 shows the most promising RFS estimate in indirect comparison, but superiority over injectable agents cannot be confirmed without head-to-head randomized evidence."

Retrospective data • Review • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Phase I/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R/R AML (ASH 2024) - P1/2 | "ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors). Conclusions : The all-oral combination SAVE results in high rates of remission in pts with R/R AML with KMT2Ar, NPM1mt or NUP98r. In addition to the R/R cohort, a frontline cohort is now enrolling pts."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Metabolic Disorders • Nephrology • Neutropenia • Oncology • Renal Disease • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

Long-Term Follow-Up of Oral Decitabine/Cedazuridine (ASTX727) Plus Venetoclax in Older or Unfit Patients With Newly Diagnosed Acute Myeloid Leukemia (SOHO 2026) - "Oral decitabine/cedazuridine plus venetoclax is an effective oral treatment for older/unfit patients with NDAML. Response rates were higher in de novo NDAML, whereas survival differences between groups were not statistically significant. AML: acute myeloid leukemia, CIR: cumulative incidence of relapse, CR: complete response, CRi: complete remission with incomplete hematologic recovery, ECOG PS: Eastern Cooperative Oncology Group performance status, MRD: minimal residual disease, NDAML: newly diagnosed acute myeloid leukemia, NRM: nonrelapse mortality, ORR: objective response rate, OS: overall survival, RFS: relapse-free survival, TP53: tumor protein p53."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Clinical Outcomes Using Frontline “Triplet“ Regimens for Newly Diagnosed IDH-Mutated Acute Myeloid Leukemia (AML): A Pooled Analysis of Two Phase Ib/2 Clinical Trials (ASH 2024) - P1/2 | "Targeted IDH inhibitors (IDHi) such as ivosidenib (IVO) and enasidenib (ENA) are also effective, either as single agents or in combination with azacitidine (AZA)...In this pooled analysis, we report the clinical outcomes and patterns of relapse among pts with newly diagnosed (ND) IDH mutant AML who are not eligible for intensive chemotherapy treated with frontline triplet regimens containing a HMA + venetoclax (VEN) + IDHi...Pts received either frontline AZA + VEN + IVO or oral Decitabine/Cedazuridine (ASTX727) + VEN + IVO/ENA (arms for IDH1 or IDH2 mutant disease, respectively)...Given these promising frontline results, prospective studies comparing triplet versus doublet regimens for IDH mutant AML are warranted. Enrollment on both HMA + VEN + IDHi triplet trials is ongoing."

Clinical data • Retrospective data • Acute Myelogenous Leukemia • Hepatology • Mucositis • ETNK1 • FLT3 • GNAS • IDH1 • IDH2 • KRAS • NPM1 • NRAS • SETBP1 • TET2 • TP53