Phase 1 Study Explores Entinostat With Nivo/Ipi in HER2-Negative Breast Cancer

Evanthia Roussos Torres, MD, PhD, an assistant professor of medicine at the University of Southern California Keck School of Medicine, discusses the study design of the phase 1 trail (NCT02453620) evaluating entinostat (SNDX-275), nivolumab (Opdivo), and ipilimumab (Yervoy) in patients with locally advanced or metastatic HER2-negative breast cancer that cannot be removed by surgery.

According to Torres, the phase 1 portion of the trial found the triplet combination to be safe, with expected adverse events. The overall response rate for the first part of the study was 16% in the initial cohort. Responses were seen in both patients with triple-negative breast cancer and hormone-receptor positive breast cancer.

The second part of the study contained a cohort of patients with advanced HER2-negative breast cancer with no prior immune checkpoint inhibition. Patients were first given a run-in of entinostat for 2 weeks. After the run-in was completed, patients received nivolumab and ipilimumab. Over the course of the 8-week treatment, 3 blood draws were completed at different intervals.

0:08 | The first part of the phase one trial was recently published in Clinical Cancer Research as a phase 1 trial to test the safety of this novel combination in patients with advanced solid tumors. Our recent publication of the results reported that this treatment combination is actually associated with expected adverse events for these agents and a recommended phase 2 dose was identified. An overall response rate of 16% was observed in this initial cohort, including responses in triple-negative breast cancer and hormone-receptor positive breast cancer. And correlative studies from the initial phase 1 trial show that an increase in CDA to T regulatory ratio was noted after combination therapy. So that was the first part of the study.

0:47 | The second part of the study which we're presenting here, was designed similarly, in which the cohort was specifically breast cancer. So, the cohort was advanced HER2-negative breast cancer with no prior immune checkpoint inhibition. Then patients were enrolled and were given what we call a run-in of entinostat, which they got for 2 weeks, followed by the addition of nivolumab and ipilimumab. And the combination of entinostat, nivolumab, and ipilimumab again is the recommended phase 2 dose that was determined from the first dose escalation cohort. And that's 3 mix per week of the entinostat, nivolumab at 3 milligrams per kilogram twice for two weeks, and ipilimumab at 1 milligram per kilogram for 6 weeks with a maximum of 4 doses. We had 3 biopsy and blood draws, 1 prior to starting entinostat, 1 after the 2-week run-in of entinostat, and 1 at the end of the 8-week treatment with the combination therapies. And after that we had the ability to do some of the correlate of results.