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
Key claim: A Phase I/II trial is evaluating the combination of the ERK inhibitor ASTX029 with oral decitabine/cedazuridine (ASTX727) to establish a safe dose and assess disease control in patients with RAS pathway-mutant MDS or MDS/MPN.
Abstract
The goal of Part 1 of this clinical research study is to find the highest tolerable dose of ASTX029 that can be given in combination with ASTX727 to participants who have RAS-mutant MDS or MDS/MPN. The goal of Part 2 of this clinical research study is to learn if the dose of ASTX029 found in Part 1 can help to control the disease when used in combination with ASTX727.
Why this matters
RAS pathway mutations are enriched in CMML and other MDS/MPN overlap entities and drive ERK/MAPK signaling dependence, yet no approved targeted therapy exploits this vulnerability. This first-in-class combination of an ERK inhibitor with oral decitabine/cedazuridine represents a genotype-directed strategy layered onto an HMA backbone, potentially establishing a new precision-medicine axis for a subtype where treatment has historically been extrapolated from MDS.