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

Inclusion Criteria: * Age ≥ 18 years as MDS and MDS/MPN are a very rare disease in the pediatric setting. * Diagnosis of MDS or MDS/MPN (including CMML, aCML, MDS/MPN-U) according to WHO and: * Initial phase 1 cohorts (cohorts A): MDS participants with no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 or relapse or progression after any number of cycles OR MDS/MPN relapsed/refractory following treatment with hydroxyurea OR at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with hydroxiurea. * Phase 2 dose expansion cohort: * Relapsed MDS cohort (Cohort B): no response after 4 cycles of azacitidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles. * Relapsed MDS/MPN cohort (Cohort C): relapsed/refractory following treatment with hydroxyurea or at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with wih hydroxiurea. * Known mutation in genes leading to RAS pathway activation (NRAS, KRAS, BRAF, CBL, NF1, PTPN11). * Creatinine clearance ≥30ml/min based on the Cockcroft-Gault Glomerular Filtration Rate estimation. * Adequate hepatic function with total bilirubin ≤1.5x ULN, AST or ALT ≤3 xULN. * ECOG Performance Status 0-2. * Participant (or patient's legally authorized representat…