Inqovi (decitabine/cedazuridine) / Otsuka - LARVOL DELTA

NIBIT-ML-1: A randomized, run-in, phase II study of nivolumab combined with ipilimumab and oral decitabine/cedazuridine (ASTX727) or nivolumab combined with ipilimumab in melanoma and NSCLC patients resistant to anti-PD-1/PD-L1 (clinicaltrialsregister.eu) - P1/2 | N=148 | Recruiting | Sponsor: Fondazione NIBIT Onlus | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • ROS1

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 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

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

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

CELESTIAL-MDS: Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Clinical Hub for Interventional Research (CHOIR) | Trial primary completion date: Dec 2025 ➔ Aug 2026

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

ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1 (clinicaltrials.gov) - P1/2 | N=31 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

New P1/2 trial • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

PRAC adopted an extension of indication for INAQOVI in combination with venetoclax for adults with newly diagnosed acute myeloid leukemia ineligible for standard induction chemotherapy, based on interim results from the ASTX727-07 study. SmPC sections 4.1, 4.2, 4.8, 5.1 and 5.2 were updated accordingly. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 12 – 15 Jan 2026: [AI generated summary]

PRAC • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Inqovi: PDUFA action date for AML May 25, 2026 (Otsuka) - FY2025 Results

PDUFA • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Leukemia Cutis: Clinicopathologic and Genomic Correlation in Skin–Marrow Pairs (USCAP 2026) - "Most c-AML cases (80%) received 7+3 chemotherapy while CMN treatments varied, including inqovi, tyrosine kinase inhibitors, hypomethylating agents alone or with venetoclax...Results Table: Table 1: Clinicopathologic and Genomic Correlation among myeloid neoplasms (acute and chronic) involving skin and bone marrow BM- bone marrow, CML- chronic myeloid leukemia, MPN- myeloproliferative neoplasm, CMML- chronic myelomonocytic leukemia, a CML- atypical chronic myeloid leukemia, BCR::ABL1 negative, MDS/MPN- myelodysplastic/myeloproliferative neoplasm, MDS- myelodysplastic syndrome, WBC- white blood cell count, Hb- hemoglobin, PLT- platelet count, MR-myelodysplasia related, NOS- not otherwise specified, 7 + 3 therapy- cytarabine + anthracycline, HMA- hypomethlating agents, Ven-venetoclax, FLAG-Ida-Ven- fludarabine + cytarabine+ granulocyte colony-stimulating factor (G-CSF)+ idarubicin+ venetoclax, TKI-tyrosine kinase inhibitor, BMT-bone marrow transplant, CR- clinical..."

Clinical • Acute Myelogenous Leukemia • Atypical Chronic Myeloid Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • ABL1 • ASXL1 • DNMT3A • ETV6 • FLT3 • JAK2 • KMT2A • KRAS • NPM1 • NRAS • PTPN11 • RUNX1 • TET2 • TP53 • WT1

ETCTN: Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jan 2027

Trial completion date • Oncology • Sarcoma • Solid Tumor

Comparing Different Treatment Lengths for Venetoclax in Older People With Newly Diagnosed Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=126 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • ABL1 • BCR • PML

DECISIVO: A study to evaluate the safety and efficacy of oral decitabine plus ivosidenib in newly diagnosed adult patients with acute myeloid leukemia older than 60 years and/or inelegible for standard induction chemotherapy (clinicaltrialsregister.eu) - P1/2 | N=50 | Not yet recruiting | Sponsor: Fundacion PETHEMA

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-MARRO) (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: Michael Savona | Trial completion date: Aug 2025 ➔ Dec 2027 | Trial primary completion date: Aug 2024 ➔ Aug 2027

Trial completion date • Trial primary completion date • Myelodysplastic Syndrome

Oral decitabine and cedazuridine maintenance after haematopoietic stem-cell transplantation in very high-risk acute myeloid leukaemia or myelodysplastic syndrome (GFM-DACORAL-DLI): a multicentre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "ASTX727 could be a potential treatment option after HSCT in patients with acute myeloid leukaemia or myelodysplastic syndrome at very high risk of relapse. Further investigation is warranted to establish the efficacy and safety of this therapeutic approach."

Journal • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Mechanisms Underlying Cedazuridine-Mediated Enhancement of Oral Decitabine Bioavailability. (PubMed, Cancer Res Commun) - "CNT1 KO mice given decitabine with cedazuridine showed ~60% lower AUC and ~1.8-fold higher urinary loss than WT mice. Our results demonstrate that cedazuridine prevents extensive first-pass metabolism of decitabine primarily through CDA inhibition but also enhances renal elimination by affecting CNT1-mediated tubular reabsorption, thereby highlighting renal transport as a source of pharmacokinetic drug-drug interactions with decitabine."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • 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) | Suspended ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • ABL1 • BCR • IDH2

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) | Initiation date: Apr 2026 ➔ Oct 2026

Trial initiation date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD4

Pacritinib With Standard of Care Azacitidine or Decitabine as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant for Patients With Accelerated and Blast Phase Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Enrollment open • Bone Marrow Transplantation • Essential Thrombocythemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

ASTX660-03: A Study of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma (R/R PTCL) (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Phase classification: P1/2 ➔ P1 | Trial completion date: Dec 2026 ➔ Mar 2026

Phase classification • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Real-world study of use patterns and clinical outcomes for patients with myelodysplastic syndrome initiating oral decitabine and cedazuridine or intravenous/subcutaneous hypomethylating agents. (PubMed, Ther Adv Hematol) - "The other HMAs approved for MDS, decitabine and azacitidine, are administered intravenously (IV) or subcutaneously (SC). While study results indicate comparable rwOS and AML-free survival among patients treated with oral DEC-C or with IV/SC HMAs, patients treated with oral DEC-C had a significantly longer rwTTNT. These findings support the use of oral DEC-C as an alternative to parenteral HMA therapy."

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

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

Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Pamela Munster | Trial completion date: Feb 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

Trial completion date • Trial primary completion date • Myelodysplastic Syndrome • BRCA • BRCA1 • BRCA2 • CHEK2

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

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) | Trial completion date: Jan 2026 ➔ Jan 2027 | Initiation date: Oct 2025 ➔ Apr 2026 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial initiation date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD4