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.

我们报告了 24 名女性的结果，其中 50%（N  = 12）患有激素受体阳性乳腺癌，50%（N  = 12）患有晚期三阴性乳腺癌，从剂量递增开始接受恩替司他 + 纳武单抗 + 伊匹单抗治疗（N  = 6) 和 ETCTN-9844 (NCT02453620) 的扩展队列 ( N  = 18)。主要终点是安全性。次要终点是总体缓解率、临床获益率、无进展生存期和肿瘤 CD8:FoxP3 比率的变化。没有剂量限制性毒性。在可评估的参与者 ( N  = 20) 中，总体缓解率为 25% ( N  = 5)， 其中三阴性乳腺癌为40% ( N = 4)， 激素受体阳性乳腺癌为10% ( N = 1)癌症。临床获益率为 40%（N  = 8），6 个月无进展生存率为 50%。探索性分析表明，骨髓细胞的变化可能有助于反应；然而，CD8:FoxP3 比率的变化、PD-L1 状态与肿瘤突变负荷和反应之间没有相关性。这些发现支持在 II 期试验中进一步研究这种治疗方法。