Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.

ABSTRACT:

Purpose

Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models.

Experimental design

This was a phase 1 dose-escalation study of belinostat and adavosertib in patients with relapsed/refractory AML and myelodysplastic syndrome (MDS). Patients received both drugs on days 1-5 and 8-12 of a 21-day cycle. Safety and toxicity were monitored throughout the study. Plasma levels of both drugs were measured for pharmacokinetic analysis. Response was determined by standard criteria including bone marrow biopsy.

Results

Twenty patients were e

SUBMITTER: Shafer D 

PROVIDER: S-EPMC10807611 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature