Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial

We report the results of 24 women, 50% ( N = 12) with hormone receptor-positive breast cancer and 50% ( N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation ( N = 6) and expansion cohort ( N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants ( N = 20), the overall response rate was 25% ( N = 5), with 40% ( N = 4) in triple-negative breast cancer and 10% ( N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% ( N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.