Syndax Pharmaceuticals Presents Updated Phase 2 Data from ENCORE 601 Trial of Entinostat in Combination with KEYTRUDA® (pembrolizumab) at the American Association for Cancer Research 2019 Annual Meeting
"We are very pleased to report that updated findings announced today continue to support our prior observation that the addition of entinostat to pembrolizumab may overcome resistance in a subset of melanoma and NSCLC patients who are refractory to anti-PD-1 therapy," said
During an oral presentation today titled, "Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma previously treated with anti-PD1 therapy",
Correlative analyses consistent with entinostat's hypothesized mechanism of action indicate a trend in decreased circulating myeloid derived suppressor cells (MDSCs) and increased CD8+ T cells in responding patients. Gene expression changes in post-treatment tumor biopsy samples in responders versus non-responders support up-regulated immune response signatures and down-regulation of immune resistance pathways.
During an oral presentation on Sunday titled, "Identification of gene signatures associated with response in a Phase 2 trial of entinostat (ENT) plus pembrolizumab (PEMBRO) in non-small cell lung cancer (NSCLC) patients whose disease has progressed on or after anti-PD-(L)1 therapy",
Results from gene set analyses revealed a significantly enriched Myc regulated gene signature in responders versus non-responders. Multiple studies have implicated elevated Myc signaling as a resistance factor to anti-PD-(L)1 therapy1-3, and separately have shown that entinostat can downregulate Myc activity4,5. These findings provide further insight into the potential mechanistic basis for response to the entinostat-pembrolizumab combination treatment in PD-(L)1 pretreated patients.
Entinostat, Syndax's selective, oral, once-weekly inhibitor of class I histone deacetylases (HDACs), has been shown to resensitize Hormone Receptor positive (HR+) advanced breast cancer to endocrine therapy, and is currently being evaluated in a pivotal Phase 3 clinical trial in combination with exemestane for advanced HR+ breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the
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This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend," "believe" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials and the reporting of clinical data for Syndax's product candidates, the potential use of our product candidates to treat various cancer indications. Many factors may cause differences between current expectations and actual results including unexpected safety or efficacy data observed during preclinical or clinical trials, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of Syndax's collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the
1. Topper MJ, et al. Cell. 2017; 171: 1284-1300
2. Jerby-Arnon L, et al. Cell. 175: P984-997
3. Kortlever RM, et al. Cell. 2017; 171: 1301-1315
4. Simmons JK, et al. Mol Cancer Ther. 2017; 16: 2008-2021
5. Nebbioso A, et al.
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