Sequencing analysis reveals evidence of immune activation in advanced HER2 negative breast cancer responders treated with entinostat + nivolumab + ipilimumab.

ABSTRACT: We analyzed the pathways associated with therapeutic response in 19 patients (5 responders) enrolled in a Phase Ib trial (NCT02453620) diagnosed with advanced HER2-negative breast cancer and treated with the HDAC inhibitor entinostat, in combination with dual immune checkpoint inhibitors (ICIs), nivolumab and ipilimumab. The analysis included gene expression and T-cell receptor (TCR) repertoire data derived from bulk RNA-seq and neoantigen data from whole exome sequencing. A total of 37 tumor biopsies were taken from six different metastatic sites at three timepoints: before treatment (baseline), after a two-week entinostat run-in (C1D1), and after the dual ICIs were added (week 8). Paired differential gene expression (DE) analysis between different timepoints revealed changes in immune-re

SUBMITTER: Torres ER 

PROVIDER: S-EPMC12204493 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature