Next Steps After Trial of Entinostat for Advanced Breast Cancer

Evanthia Roussos Torres, MD, PhD, assistant professor of medicine at the University of Southern California Keck School of Medicine, discusses the follow-up research related to the phase 1 study (NCT02453620) of entinostat (MS-275) administered in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of locally advanced, metastatic, unresectable, or HER2-negative breast cancer.

The phase 1 trial explored the use of entinostat, a histone deacetylase inhibitor which can reduce tumor growth by targeting enzymes, along with the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitor nivolumab. The initial trial of 24 patients with multiple types of advanced breast cancer of determined a recommended safe dosage for the phase 2 trial and gathered other promising data on the efficacy and safety of the combination.

According to Torres, she and other investigators intend to analyze correlative results to evaluate the immune response. Areas of interest include bulk RNA sequencing, B-cell and T-cell receptor sequencing, and myeloid cell populations in patients before and after they received the combination including entinostat.

They intend to continue researching the immune cell types and molecular mechanisms that could be linked to the responses to the combination therapy as they work to expand the trial in phase 2. Better understanding of the mechanism of action could improve the targeting of therapies toward certain biomarkers, Torres explains.

TRANSCRIPTION:

0:08 | We have a number of correlative results that…we've just started analyzing. We're going to be looking at some of the bulk RNA sequencing and B-cell receptor and T-cell receptor sequencing as well as using imaging mass cytometry to investigate the myeloid cell populations in patient specimens after the entinostat and after the addition of checkpoint inhibition, because we feel that there are multiple other immune cell types that are affected by the therapy that are likely responsible for the responses that we're seeing. In addition, we were looking forward to planning the next phase results; given the promising results we've seen here, we think there are more patients with breast cancer who can benefit from this novel combination therapy.

0:52 | My lab is focusing on understanding the mechanisms of response to entinostat plus [immune] checkpoint inhibition in breast cancer. We're doing a lot of the preclinical work that goes along in parallel with what we're doing in the clinical trials, so that we can better understand specific molecular mechanisms that entinostat is imparting on some of these important immune cell types to potentially provide data that would support even more specific therapies or help with biomarkers to select patients who are most likely to respond.