NCT06284460

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

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Primary Objectives: * Phase 1 dose escalation: to determine safety, tolerability and MTD of ASTX029 in RAS mutant MDS, CMML and other MDS/MPN * Phase 2 dose expansion: to determine the safety, tolerability and overall response rate (ORR) of ASTX727 in combination with ASTX029 in RAS mutant MDS, CMML and other MDS/MPN * Incidence of AEs, MTD and changes in clinical laboratory values. * Measures of efficacy: overall response rate (ORR) defined as sum of CR + complete cytogenetic remission + partial remission + marrow response + clinical benefit for MDS/MPN and defined as CR + mCR + PR + HI in MDS Secondary Objectives: * To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall survival (OS). * To evaluate differences in response and efficacy outcomes by MDS/MPN IWG response criteria based on disease subtypes and genomic features. * Correlative studies * To evaluate changes in clonal composition and VAF of identified mutations with therapy. * To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ASTX029 and the combination of ASTX727 with ASTX029 in patients with RAS mutant MDS, CMML and other MDS/MPN

Conditions

• Pathway Mutant Myelodysplastic Syndromes
• Myelodysplastic Neoplasm
• Myeloproliferative Neoplasm

Interventions

Type	Name	Description
DRUG	ASTX029	Given by PO
DRUG	ASTX727	Given by PO

Timeline

• Start date: 2025-01-31
• Primary completion: 2025-12-01
• Completion: 2027-12-01
• First posted: 2024-02-29
• Last updated: 2026-02-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study