ASTX727 (oral cedazuridine + decitabine)

Current understanding

To be populated as evidence accumulates.

Evidence log

• 2026-09-21 — Metronomic Decitabine-Cedazuridine and Venetoclax in R/R AML, HR-MDS, HR/AP MPN: Phase 2 randomized trial (trial-early) tests metronomic (low-dose continuous) ASTX727 + venetoclax in R/R AML, HR-MDS, and high-risk/accelerated-phase MPN — first evaluation of a metronomic ASTX727 schedule as the oral HMA backbone in a salvage setting spanning MPN blast/accelerated phase. (novelty: 3)
• 2026-06-08 — Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent: Tangentially related: an early-phase trial (trial-early) of recombinant EphB4-HSA fusion protein combined with parenteral azacitidine or decitabine in HMA-refractory MDS/CMML/AML reinforces the role of HMA backbones as a partner for novel mechanism-targeted agents in HMA-failure populations, though using parenteral rather than oral cedazuridine-decitabine formulation. (novelty: 4)
• 2026-06-11 — Venetoclax in Combination With ASTX727 for the Treatment of Treatment-Naive High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia: Phase I/II trial (trial-early) of ASTX727 + venetoclax in treatment-naive high-risk MDS/CMML reinforces ASTX727’s role as the oral HMA backbone for frontline BCL-2 inhibitor combinations in the overlap-syndrome population. (novelty: 3)
• 2026-05-15 — Chemotherapy (Decitabine in Combination With FLAG-Ida) and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Adults With Myeloid Malignancies at High Risk of Relapse: Tangentially related: a phase I/II trial (trial-early) of parenteral decitabine added to FLAG-Ida + TBI as pre-transplant conditioning in high-risk AML/MDS/CMML further establishes decitabine’s role across pre-transplant settings, though using IV decitabine rather than the oral cedazuridine-decitabine formulation. (novelty: 3)
• 2026-05-13 — Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm: Phase II randomized trial (trial-early) tests ASTX727 ± venetoclax in CMML and MDS/MPN with excess blasts, extending ASTX727’s oral HMA backbone role into BCL-2 inhibitor combinations for the overlap-syndrome population. (novelty: 3)
• 2026-03-04 — 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: Phase II trial (trial-early) tests pacritinib + standard-of-care azacitidine or decitabine as bridging therapy to allo-HSCT in AP/BP-MPN; positions HMAs (including decitabine) as the backbone partner with pacritinib in chemo-sparing bridging strategies. (novelty: 3)
• 2026-02-13 — Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms: Phase I/II trial (trial-early) combining ASTX727 with the ERK inhibitor ASTX029 in RAS pathway-mutant MDS and MDS/MPN, extending ASTX727’s role as oral HMA backbone into MAPK-pathway-targeted combinations for genomically defined subpopulations. (novelty: 4) (novelty: 4)
• 2026-03-30 — Inqovi Maintenance Therapy in Myeloid Neoplasms: Prospective trial (trial-early) evaluating ASTX727/Inqovi as post-allogeneic-transplant maintenance therapy in MDS/CMML to reduce relapse risk, extending its role beyond active-disease treatment into the maintenance setting. (novelty: 3)
• 2026-04-02 — Seclidemstat and Azacitidine for the Treatment of Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia: Related combination: a phase I/II trial (trial-early) of seclidemstat (LSD1 inhibitor) + azacitidine in MDS/CMML mirrors the LSD1i + HMA strategy being tested as ASTX727 + iadademstat in advanced MPNs, suggesting cross-disease applicability of the LSD1i + HMA backbone. (novelty: 3)
• 2026-01-28 — Combination Navitoclax, Venetoclax and Decitabine for Advanced Myeloid Neoplasms: Tangentially related: parenteral decitabine is being combined with navitoclax + venetoclax in a phase I trial for advanced myeloid neoplasms including MF, suggesting future potential for ASTX727 as oral HMA backbone in BCL-2/BCL-XL combination regimens. (novelty: 3)
• 2026-03-16 — Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms: Phase II trial (trial-early): decitabine paired with ruxolitinib, fedratinib, or pacritinib as pre-transplant bridging therapy in AP/BP-MPN, compared against multi-agent chemotherapy or no bridging — positions HMA + JAK inhibitor as a chemo-sparing bridge to allo-SCT. (novelty: 3)
• 2026-04-28 — A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs): Phase II randomized trial (trial-early) evaluating ASTX727 monotherapy vs. ASTX727 + iadademstat in accelerated/blast phase Ph-negative MPNs, positioning ASTX727 as backbone oral HMA therapy in this high-risk setting. (novelty: 4)

Open questions

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